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Zeng D, Wang Y, Wen N, Li B, Cheng N, Lu J. Short-term and Long-term Clinical Outcomes of Combined Caudate Lobectomy for Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus: A Propensity Score Analysis. Gut Liver 2025; 19:438-453. [PMID: 39327842 PMCID: PMC12070214 DOI: 10.5009/gnl240158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/31/2024] [Accepted: 06/09/2024] [Indexed: 09/28/2024] Open
Abstract
Background/Aims Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.
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Affiliation(s)
- Di Zeng
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yaoqun Wang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ningyuan Wen
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Nansheng Cheng
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Jiong Lu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
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Chen R, Tang T, Han J, Li S, Liu W, Deng H, Jian T, Fu Z. Temporal trends of the disease burden of renal cell carcinoma from 1992 to 2019 in the US: a population-based analysis. Cancer Causes Control 2025:10.1007/s10552-025-02007-1. [PMID: 40358845 DOI: 10.1007/s10552-025-02007-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 04/30/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE Significant advances in the management, in particular the treatment, of renal cell carcinoma (RCC) has have been made over the years. However, it is not clear whether these advances reduce the disease burden of RCC at the population level. METHODS Using data from the Surveillance, Epidemiology, and End Results database, we estimated the temporal trends of RCC incidence, incidence-based mortality (IBM), and survival rates in the United States (US) from 1992 to 2019. RESULTS From 2008 to 2019, the incidence increased slowly at 1.1% annually (95% CI: 0.6% to 1.5%). The overall IBM rate of RCC increased by 6.8% per year (95% CI: - 1.1% to 15.3%) between 1994 and 1997, plateaued between 1997 and 2015, and then decreased nonsignificantly after 2015. During the study period, the overall Five year survival rate of RCC continuously increased from 53.69 in 1992 to 72.90% in 2014, with the best improvement observed for RCC patients with distant disease. However, we projected that, given the current trends, the incidence of RCC in the US will continue to increase from 6.92 per 100,000 in 2015-2019 to 9.59 per 100,000 in 2040-2044. CONCLUSION Over the years, the mortality of RCC has been decreased reducing at the US population level mainly because the considerably significantly improved survival of RCC patients at all stages through the advances in treatment. However, the overall incidence of RCC is continuously increasing, indicating that more effective preventive strategies should be developed to reduce the disease burden of RCC.
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Affiliation(s)
- Ruyan Chen
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Tian Tang
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Jianglong Han
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Si Li
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Wenmin Liu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Haiyu Deng
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Tingting Jian
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Zhenming Fu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
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Ding Y, Luan W, Lu F, Wang Z, Shen X. SNHG19 promotes the proliferation and metastasis of hepatocellular carcinoma through regulating the miR-137/protein tyrosine phosphatase 4A3 axis. SAGE Open Med 2025; 13:20503121251334272. [PMID: 40297784 PMCID: PMC12035070 DOI: 10.1177/20503121251334272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/26/2025] [Indexed: 04/30/2025] Open
Abstract
Objectives Long noncoding RNAs plays the important part in tumor biology. SNHG19 was found to be a new oncogenic lncRNA in some malignant tumors. However, the effect of SNHG19 in hepatocellular carcinoma has not been reported. Methods The expression of SNHG19 in hepatocellular carcinoma tissues were detected by using quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Melanoma cases from The Cancer Genome Atlas were included in this study. cell counting kit-8 assay, Transwell, and scratch wound assay were used to explore the role of SNHG19 in melanoma cells. Luciferase reporter assays and RNA pull-down assay were used to explore the molecular mechanism of SNHG19 in hepatocellular carcinoma. Results Here, we found that SNHG19 level was upregulated in hepatocellular carcinoma. Hepatocellular carcinoma patients with high levels of SNHG19 have shorter Disease-Free Survival (RFS). SNHG19 promotes the Protein Tyrosine Phosphatase 4A3 expression by sponging miR-137 to liberate Protein Tyrosine Phosphatase 4A3 mRNA transcripts. SNHG19 enhances the development of hepatocellular carcinoma by affecting miR-137/Protein Tyrosine Phosphatase 4A3 axis. Conclusion These results demonstrated the effect of SNHG19 in the occurrence and progression of hepatocellular carcinoma. SNHG19 may be used as the specific molecular target in patients with hepatocellular carcinoma.
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Affiliation(s)
- Yuting Ding
- Department of Rehabilitation, Changshu No. 2 People’s Hospital (Changshu Hospital Affiliated the NanTong University), Jiangsu, China
| | - Wenkang Luan
- Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Lu
- Department of Plastic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang First People’s Hospital, China
| | - Zhe Wang
- Human Anatomy and Histoembryology Laboratory, Jiangsu University, Zhenjiang, China
| | - Xuanlin Shen
- Department of Rehabilitation, Changshu No. 2 People’s Hospital (Changshu Hospital Affiliated the NanTong University), Jiangsu, China
- Cancer Institute, Xuzhou Medical University, Jiangsu, China
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Kim SS, Lee J, Ahn SB, Chon YE, Yoon E, Jeong SW, Jun DW. Clinical Course and Prognosis of Long-Term Survivors of Hepatocellular Carcinoma. Aliment Pharmacol Ther 2025; 61:1333-1342. [PMID: 39955712 DOI: 10.1111/apt.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 08/25/2024] [Accepted: 01/22/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND AND AIMS This study investigated the long-term prognosis and clinical course of patients who survived for more than 5 years after hepatocellular carcinoma (HCC) diagnosis. METHODS This retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 35,348 subjects newly diagnosed with HCC between January 2008 and December 2010 were followed up until December 2018. RESULTS A total of 11,514 (32.6%) survived for 5 years after diagnosis of HCC among 35,348 patients diagnosed with HCC. Long-term survivors (≥ 5 years) had a higher proportion of females, younger age, more frequent aetiology of hepatitis B virus, less frequent liver cirrhosis, diabetes mellitus and hypertension, and received curative treatment more frequently than nonsurvivors (< 5 years). The additional 1-, 3- and 5-year cumulative survival probabilities were 90.7%, 77.6% and 68.4% respectively. Patients who underwent curative treatment as the first treatment for HCC showed a higher additional 5-year cumulative survival probabilities than those treated with noncurative therapy (74.5% vs. 64.2%). Among the long-term survivors, 44.4% underwent HCC retreatment 5 years after HCC diagnosis. The additional 5-year cumulative survival probability was 54.9% in the HCC retreatment group. The overall 5- and 10-year cumulative probabilities of second primary malignancies in long-term survivors were 15.36% and 27.54% respectively. The most frequent second primary malignancy was prostate cancer, followed by colorectal and pancreatic cancers. CONCLUSION Our study highlights that a significant proportion of patients with HCC achieve long-term survival beyond 5 years, with favourable outcomes associated with curative treatments.
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Affiliation(s)
- Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Jonghyun Lee
- Department of Medical and Digital Engineering, Hanyang University College of Engineering, Seoul, South Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Eulji University College of Medicine, Seoul, South Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | - Eileen Yoon
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Dae Won Jun
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul, South Korea
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Kong Q, Li K. Predicting early recurrence of hepatocellular carcinoma after thermal ablation based on longitudinal MRI with a deep learning approach. Oncologist 2025; 30:oyaf013. [PMID: 40110765 PMCID: PMC11923588 DOI: 10.1093/oncolo/oyaf013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/13/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Accurate prediction of early recurrence (ER) is essential to improve the prognosis of patients with hepatocellular carcinoma (HCC) underwent thermal ablation (TA). Therefore, a deep learning model system using longitudinal magnetic resonance imaging (MRI) was developed to predict ER of patients with HCC. METHODS From 2014, April to 2017, May, a total of 289 eligible patients with HCC underwent TA were retrospectively enrolled from 3 hospitals and assigned into one training cohort (n = 254) and one external testing cohort (n = 35). Two deep learning models (Pre and PrePost) were developed using the pre-operative MRI and longitudinal MRI (pre- and post-operative) to predict ER for the patients with HCC after TA, respectively. Then, an integrated model (DL_Clinical) incorporating PrePost model signature and clinical variables was built for post-ablation ER risk stratification for the patients with HCC. RESULTS In the external testing cohort, the area under the receiver operating characteristic curve (AUC) of the DL_Clinical model was better than that of the Clinical (0.740 vs 0.571), Pre (0.740 vs 0.648), and PrePost model (0.740 vs 0.689). Additionally, there was a significant difference in RFS between the high- and low-risk groups which were divided by the DL_Clinical model (P = .04). CONCLUSIONS The PrePost model developed using longitudinal MRI showed outstanding performance for predicting post-ablation ER of HCC. The DL_Clinical model could stratify the patients into high- and low-risk groups, which may help physicians in treatment and surveillance strategy selection in clinical practice.
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Affiliation(s)
- Qingyang Kong
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Kai Li
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
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Tang L, Yang X, He L, Zhu C, Chen Q. Preclinical advance in nanoliposome-mediated photothermal therapy in liver cancer. Lipids Health Dis 2025; 24:31. [PMID: 39891269 PMCID: PMC11783920 DOI: 10.1186/s12944-024-02429-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/31/2024] [Indexed: 02/03/2025] Open
Abstract
Liver cancer is a highly lethal malignant tumor with a high incidence worldwide. Therefore, its treatment has long been a focus of medical research. Although traditional treatment methods such as surgery, radiotherapy, and chemotherapy have increased the survival rate of patients, their efficacy remains unsatisfactory owing to the nonspecific distribution of drugs, high toxicity, and drug resistance of tumor tissues. In recent years, the application of nanotechnology in the medical field has opened a new avenue for the treatment of liver cancer. Among these treatment methods, photothermal therapy (PTT) based on nanoliposomes has attracted wide attention owing to its unique targeting and high efficiency. This article reviews the latest preclinical research progress of nanoliposome-based PTT for liver cancer and its metastasis, discusses the preclinical challenges in this field, and proposes directions for improvement, with the aim of improving the effectiveness of liver cancer treatment.
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Affiliation(s)
- Lixuan Tang
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Xiao Yang
- The department of oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Liwen He
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Chaogeng Zhu
- The department of hepatobiliary pancreatic hernia surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China.
| | - Qingshan Chen
- The department of hepatobiliary pancreatic hernia surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China.
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Liu Y, Zhang X, Hao J, Zhao Y, Zou M, Chen H, Zhang J. Essential oils from Amorpha fruticosa against hepatocellular carcinoma based on network pharmacology. BMC Complement Med Ther 2025; 25:29. [PMID: 39871242 PMCID: PMC11771004 DOI: 10.1186/s12906-025-04766-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 01/16/2025] [Indexed: 01/29/2025] Open
Abstract
BACKGROUND Amorpha fruticosa was used for treating burn, ambustion, carbuncle, and eczema in the traditional Chinese medicine. Although more and more attention has been paid to its biological activity recently, the antitumor activities of the essential oils (EOs) extracted from its leaves (AFLEO) and flowers (AFFEO), and their molecular mechanisms have never been reported up to now. The objective of present study was to examine the chemical compositions of AFLEO and AFFEO, then investigate the effects and pharmacological mechanism of EOs against hepatocellular carcinoma (HCC). METHODS The chemical compositions of EOs were examined using gas chromatography-mass spectrometry (GC-MS). The inhibitory effect of the EOs on HCC was evaluated by MTT assay. The detected components of AFLEO and AFFEO were performed ADME screening to examine their drug-likeness. Then a PPI network, compound-target network, compound-target-pathway network, gene ontology, and KEGG enrichment for HCC were applied to identify the targets and pathways for AFLEO and AFFEO against HCC. Molecular docking of the main components and their targets was performed to predict the binding affinity. Western blotting was used to verify the results. RESULTS 30 components were identified from AFLEO, while 22 components from AFFEO. Both AFLEO and AFFEO inhibited the proliferation of HCC cells in a time and dose-dependent manner. 10 compounds of AFLEO and 9 compounds of AFFEO were screened out for further analysis. 28 hub targets of AFLEO and 40 hub targets of AFFEO were detected by PPI network. KEGG analysis revealed that pathways in cancer, chemical carcinogenesis - receptor activation and proteoglycans in cancer were related to the EOs against HCC. Molecular docking confirmed that the main component of the EOs has high affinity to the targets of HCC. CONCLUSIONS AFLEO and AFFEO may suppress HCC by acting on multiple targets and regulating multiple pathways.
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Affiliation(s)
- Yixian Liu
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xiaojun Zhang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jiacong Hao
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Ying Zhao
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Min Zou
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Huiping Chen
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
| | - Jintao Zhang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
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Tian Y, Wang Y, Wen N, Lin Y, Liu G, Li B. Development and validation of nomogram to predict overall survival and disease-free survival after surgical resection in elderly patients with hepatocellular carcinoma. Front Oncol 2024; 14:1395740. [PMID: 38854717 PMCID: PMC11157056 DOI: 10.3389/fonc.2024.1395740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/06/2024] [Indexed: 06/11/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery. Method We retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators. Result A total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA. Conclusion The nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.
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Affiliation(s)
- Yuan Tian
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yaoqun Wang
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ningyuan Wen
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yixin Lin
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Geng Liu
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Li
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
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DiStefano JK, Piras IS, Wu X, Sharma R, Garcia-Mansfield K, Willey M, Lovell B, Pirrotte P, Olson ML, Shaibi GQ. Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis. Clin Nutr ESPEN 2024; 60:333-342. [PMID: 38479932 PMCID: PMC10937812 DOI: 10.1016/j.clnesp.2024.02.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND Recent studies suggest that proteomic cargo of extracellular vesicles (EVs) may play a role in metabolic improvements following lifestyle interventions. However, the relationship between changes in liver fat and circulating EV-derived protein cargo following intervention remains unexplored. METHODS The study cohort comprised 18 Latino adolescents with obesity and hepatic steatosis (12 males/6 females; average age 13.3 ± 1.2 y) who underwent a six-month lifestyle intervention. EV size distribution and concentration were determined by light scattering intensity; EV protein composition was characterized by liquid chromatography tandem-mass spectrometry. RESULTS Average hepatic fat fraction (HFF) decreased 23% by the end of the intervention (12.5% [5.5] to 9.6% [4.9]; P = 0.0077). Mean EV size was smaller post-intervention compared to baseline (120.2 ± 16.4 nm to 128.4 ± 16.5 nm; P = 0.031), although the difference in mean EV concentration (1.1E+09 ± 4.1E+08 particles/mL to 1.1E+09 ± 1.8E+08 particles/mL; P = 0.656)) remained unchanged. A total of 462 proteins were identified by proteomic analysis of plasma-derived EVs from participants pre- and post-intervention, with 113 proteins showing differential abundance (56 higher and 57 lower) between the two timepoints (adj-p <0.05). Pathway analysis revealed enrichment in complement cascade, initial triggering of complement, creation of C4 and C2 activators, and regulation of complement cascade. Hepatocyte-specific EV affinity purification identified 40 proteins with suggestive (p < 0.05) differential abundance between pre- and post-intervention samples. CONCLUSIONS Circulating EV-derived proteins, particularly those associated with the complement cascade, may contribute to improvements in liver fat in response to lifestyle intervention.
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Affiliation(s)
- Johanna K DiStefano
- Diabetes and Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ, USA.
| | - Ignazio S Piras
- Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Xiumei Wu
- Diabetes and Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Ritin Sharma
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Krystine Garcia-Mansfield
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Maya Willey
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Brooke Lovell
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Patrick Pirrotte
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Micah L Olson
- Division of Endocrinology and Diabetes, Phoenix Children's, Phoenix, AZ, USA; Center for Health Promotion and Disease Prevention, Edson College of Nursing, Arizona State University, Phoenix, AZ, USA
| | - Gabriel Q Shaibi
- Division of Endocrinology and Diabetes, Phoenix Children's, Phoenix, AZ, USA; Center for Health Promotion and Disease Prevention, Edson College of Nursing, Arizona State University, Phoenix, AZ, USA
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Chiu KWH, Tan KV, Yang X, Zhu X, Shi J, Chiang CL, Chan L, Hui Y, Khong PL, Man K, Wong JWH. Prognostic PET [ 11C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study. Cancer Imaging 2024; 24:42. [PMID: 38520026 PMCID: PMC10958914 DOI: 10.1186/s40644-024-00685-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 03/08/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Positron Emission Tomography (PET) with combined [18F]-FDG and [11C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [11C]-acetate and [18F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution. RESULTS HAL-treated mice showed lower [11C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUVTLR): 2.14[2.05-2.21] vs 3.11[2.75-5.43], p = 0.02) but not [18F]-FDG (HAL-treated vs. Control, SUVTLR: 3.73[3.12-4.35] vs 3.86[3.7-5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [11C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [11C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06-0.42, p < 0.0001). CONCLUSIONS [11C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.
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Affiliation(s)
- Keith Wan Hang Chiu
- Department of Radiology and Imaging, Queen Elizabeth Hospital, Hong Kong SAR, China.
| | - Kel Vin Tan
- Department of Oncology, MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
| | - Xinxiang Yang
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Xiaoqiang Zhu
- School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Jingjing Shi
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Chi-Leung Chiang
- Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Lawrence Chan
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China
| | - Yuan Hui
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, Guangzhou, China
| | - Pek-Lan Khong
- Clinical Imaging Research Center (CIRC), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kwan Man
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Jason Wing Hon Wong
- School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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11
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Tsai YL, Yu PC, Nien HH, Lu TP. Time variation of high-risk groups for liver function deteriorations within fluctuating long-term liver function after hepatic radiotherapy in patients with hepatocellular carcinoma. Eur J Med Res 2024; 29:104. [PMID: 38326881 PMCID: PMC10848403 DOI: 10.1186/s40001-024-01692-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 01/20/2024] [Indexed: 02/09/2024] Open
Abstract
PURPOSE The purpose of this study is to find essential risk factors associated with liver function (LF) deteriorations within fluctuating long-term LF and their time-varying effects in patients with hepatocellular carcinoma (HCC) receiving hepatic radiotherapy and to identify high-risk groups for adverse LF deteriorations and their changes over time in facilitating the prevention of hepatic decompensation and the improvement of survival. MATERIALS AND METHODS A total of 133 HCC patients treated by hepatic radiotherapy were enrolled. A study design was conducted to convert posttreatment long-term LF with fluctuating levels over time to recurrent LF events using defined upgrades in a grading scale. The hazard ratios (HR) of pretreatment biochemical, demographic, clinical, and dosimetric factors in developing posttreatment LF events were estimated using the Cox model. Methodologies of the counting process approach, robust variance estimation, goodness-of-fit testing based on the Schoenfeld residuals, and time-dependent covariates in survival analysis were employed to handle the correlation within subjects and evaluate the time-varying effects during long-term follow-up. RESULTS Baseline LF score before radiotherapy and gender were significant factors. Initial HR in developing LF events was 1.17 (95% CI 1.11-1.23; P < 0.001) for each increase of baseline LF score and kept almost constant over time (HR, 1.00; 95% CI 1.00-1.01; P = 0.065). However, no difference was observed regarding initial hazards for gender (HR, 1.00; 95% CI 0.64-1.56; P = 0.994), but the hazard for women got higher monthly over time compared with men (HR, 1.04; 95% CI 1.01-1.07; P = 0.006). CONCLUSIONS High-risk groups for adverse LF deteriorations after hepatic radiotherapy may change over time. Patients with poor baseline LF are vulnerable from the beginning. Women require prevention strategies and careful monitoring for deteriorations at a later stage.
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Affiliation(s)
- Yu-Lun Tsai
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
| | - Pei-Chieh Yu
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Hsin-Hua Nien
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Tzu-Pin Lu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
- Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
- Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
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12
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Liang Y, Yang R, Shang J, Zhong D, Yang Q, Su Y, Shi Y, Huang X. Lung immune prognostic index‑based nomogram for recurrence of hepatocellular carcinoma after postoperative adjuvant TACE. J Cancer Res Clin Oncol 2023; 149:16461-16471. [PMID: 37707573 DOI: 10.1007/s00432-023-05413-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 09/06/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE), one of the most commonly used postoperative adjuvant therapy for HCC, has achieved satisfactory outcomes. This study aimed to explore the prognostic value of lung immune prognostic index (LIPI) and develop a novel nomogram for recurrence-free survival (RFS) of HCC patients received postoperative adjuvant TACE (PA-TACE). METHODS The prognostic value of LIPI was evaluated by C-index, receiver operating characteristic (ROC) analysis, and Kaplan-Meier survival curve. An effective nomogram based on preoperative prognostic factors was established from multivariate analysis and validated in the validation cohort. RESULTS The ROC and survival analysis demonstrated that the LIPI exhibited better prediction performance of HCC recurrence than other inflammatory biomarkers. According to univariate and multivariate analysis, LIPI, followed by AFP, MVI and age, were significant independent predictors for HCC recurrence and were utilized to construct the nomogram. The C-indexes of the nomogram were 0.746 (95% CI 0.721-0.770) and 0.738 (95% CI 0.701-0.775) in the training and validation cohort, respectively. The AUCs for the 1-, 2-, and 3-year RFS were 0.799, 0.867 and 0.884 in the training cohort and 0.798, 0.779 and 0.770 in the validation cohort, respectively. The calibration curves presented good consistencies. Moreover, compared with the LIPI and other clinical staging system, the established nomogram presented better prognostic performance. CONCLUSION Preoperative LIPI might be a powerful predictor for RFS in HCC patients received PA-TACE. The LIPI-based nomogram could further effectively predict the risk of recurrence and help clinicians formulate personalized follow-up strategies and adjuvant therapy to improve patient outcomes.
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Affiliation(s)
- Yuxin Liang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ruoyi Yang
- School of Stomatology, Guizhou Medical University, Guiyang, China
- Department of Head and Neck Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jin Shang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Deyuan Zhong
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qinyan Yang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuhao Su
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ying Shi
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Xiaolun Huang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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13
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Li J, Wang WQ, Zhu RH, Lv X, Wang JL, Liang BY, Zhang EL, Huang ZY. Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors. Front Immunol 2023; 14:1202039. [PMID: 37359534 PMCID: PMC10285103 DOI: 10.3389/fimmu.2023.1202039] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Background The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs). Methods HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted. Results A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% (P < 0.001) and 54.2% vs. 25.1% (P = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% (P = 0.001) and 84.3% vs. 55.5% (P = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT. Conclusions PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.
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Affiliation(s)
| | | | | | | | | | | | - Er-lei Zhang
- *Correspondence: Zhi-yong Huang, ; Er-lei Zhang,
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14
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Kim IY, Kim HY, Song HW, Park JO, Choi YH, Choi E. Functional enhancement of exosomes derived from NK cells by IL-15 and IL-21 synergy against hepatocellular carcinoma cells: The cytotoxicity and apoptosis in vitro study. Heliyon 2023; 9:e16962. [PMID: 37484408 PMCID: PMC10361042 DOI: 10.1016/j.heliyon.2023.e16962] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 06/02/2023] [Accepted: 06/02/2023] [Indexed: 07/25/2023] Open
Abstract
Exosomes are released by various cells, including natural killer (NK) cells and transport signaling molecules for the intercellular communication. Hepatocellular carcinoma (HCC), also known as primary liver cancer, is often inoperable and difficult to accurate diagnosis. Notably, the prognosis and underlying mechanisms of HCC are not fully understood. Exosomes-derived NK cells (NK-exos) express unique cytotoxic proteins with a killing ability in tumors and can easily penetrate tumor tissues to improve their targeting ability. NK cell functions, inducing cellular cytotoxicity are modulated by cytokines such as interleukin (IL)-15 and IL-21. However, the mechanisms and effects of cytokines-stimulated NK-exos for the treatment of liver cancer, including HCC, are not well known. In this study, we aimed to investigate the synergistic anti-tumor effects of NK-exos stimulated with IL-15 and IL-21 (NK-exosIL-15/21) in Hep3B cells. Our findings revealed that NK-exosIL-15/21 expressed cytotoxic proteins (perforin and granzyme B) and contained typical exosome markers (CD9 and CD63) within the size range of 100-150 nm. Moreover, we demonstrated that NK-exosIL-15/21 induced the enhancement of cytotoxicity and apoptotic activity in Hep3B cells by activating the specific pro-apoptotic proteins (Bax, cleaved caspase 3, cleaved PARP, perforin, and granzyme B) and inhibiting the anti-apoptotic protein (Bcl-2). In summary, our results suggest that NK-exosIL-15/21 regulate strong anti-tumor effects of HCC cells, by increasing the cytotoxicity and apoptosis through the activation of specific cytotoxic molecules.
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Affiliation(s)
- In-Young Kim
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
| | - Ho Yong Kim
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
| | - Hyeong-woo Song
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
| | - Jong-Oh Park
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
| | - You Hee Choi
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
| | - Eunpyo Choi
- Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea
- School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea
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15
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Sun L, Gu M, Cai J, Yang W, Pan B, Wang B, Zhang C, Guo W. Combining γ-GT, PIVKA-II, and AFP to predict long-term prognosis in patients with hepatocellular carcinoma after hepatectomy. Clin Exp Pharmacol Physiol 2023; 50:287-297. [PMID: 36507841 DOI: 10.1111/1440-1681.13745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/02/2022] [Accepted: 12/07/2022] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the top five contributors to the cancer burden in China, with a poor prognosis and heavy disability-adjusted life year burden. The criteria used for HCC prognosis are complicated and therefore restricted in routine clinical practice. Multiple factors influence HCC malignancy and progression. In this study, we retrospectively evaluated 173 patients with HCC who underwent curative resection for 9 years to evaluate the correlation of a combination of γ-glutamyl transferase (γ-GT), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and α-fetoprotein (AFP) with the long-term survival of patients with HCC. Multivariate analysis revealed that the γ-GT level was an independent prognostic factor for recurrence. The prediction rate of early recurrence with γ-GT, PIVKA-II, and AFP levels individually was 63.5%, 79.4%, and 39.7%, respectively, whereas the prediction rate of early recurrence was 95.2% with the combination of γ-GT, PIVKA-II, and AFP levels as a composite indicator. Our long-term retrospective study revealed that γ-GT, PIVKA-II, and AFP can aid in predicting long-term prognosis of HCC recurrence. The combination of γ-GT, PIVKA-II, and AFP can further aid in identifying patients with early recurrence. Together, γ-GT, PIVKA-II, and AFP may a be used to develop a new prediction method to improve the prognosis of patients with HCC, and our results indicate the requirement of more active HCC treatment strategies.
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Affiliation(s)
- Lin Sun
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China
| | - Meixiu Gu
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China
| | - Jiabin Cai
- Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenjing Yang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China
| | - Baishen Pan
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China.,Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.,Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Beili Wang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China.,Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.,Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chunyan Zhang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China.,Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.,Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wei Guo
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.,Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China.,Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.,Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan University, Shanghai, China
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16
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Ouyang W, Wang MD, Wang WY, Li C, Yao LQ, Zhu H, Yang T. Hydroxymethylation and Epigenetic Drugs: New Insights into the Diagnosis and Treatment in Epigenetics of Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2023; 2023:5449443. [PMID: 36816356 PMCID: PMC9934982 DOI: 10.1155/2023/5449443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/19/2022] [Accepted: 10/15/2022] [Indexed: 02/11/2023]
Abstract
Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous malignancy with multiple genetic alternations and complex signaling pathways. The complexity and multifactorial nature of HCC pose a tremendous challenge regarding its diagnosis and treatment. Emerging evidence has indicated an important regulatory role of epigenetic modifications in HCC initiation and progression. Epigenetic modifications are stably heritable gene expression traits caused by changing the accessibility of chromatin structure and genetic activity without alteration in the DNA sequence and have been gradually recognized as a hallmark of cancer. In addition, accumulating data suggest a potential value of altered hydroxymethylation in epigenetic modifications and therapeutics targeting the epigenetically mediated regulation. As such, probing the epigenetic field in the era of precision oncology is a valid avenue for promoting the accuracy of early diagnosis and improving the oncological prognosis of HCC patients. This review focuses on the diagnostic performance and clinical utility of 5-hydroxymethylated cytosine, the primary intermediate product of the demethylation process, for early HCC diagnosis and discusses the promising applications of epigenetic-based therapeutic regimens for HCC.
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Affiliation(s)
- Wei Ouyang
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
| | - Wan-Yin Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
- Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
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Cassinotto C, Nogue E, Durand Q, Panaro F, Assenat E, Dohan A, Malafaye N, Guiu B, Molinari N. Life expectancy of patients with hepatocellular carcinoma according to the upfront treatment: A nationwide analysis. Diagn Interv Imaging 2023; 104:192-199. [PMID: 36682959 DOI: 10.1016/j.diii.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 01/05/2023] [Accepted: 01/09/2023] [Indexed: 01/22/2023]
Abstract
PURPOSE The purpose of this study was to update the life expectancy of patients with hepatocellular carcinoma (HCC) in an exhaustive nationwide population according to the upfront treatment performed. MATERIALS AND METHODS From the French Program for the Medicalization of Information System database, all patients older than 18 years diagnosed with a de novo HCC from January 2011 to December 2018 were retrospectively selected. Five-year survival rates (95% confidence intervals [CI]) were computed according to the first surgical or interventional radiology procedures performed. RESULTS A total of 63,996 patients (80% men) with a median age of 68 years (Q1, Q3: 61, 77) were selected, including 24,007 patients who underwent at least one procedure (5-year survival of 45.5%; (95% CI: 44.8-46.2), and 39,989 with none (5-year survival, 9.6%; (95% CI: 9.3-10.0). Only 20.5% (13,101/63,996) of patients could undergo an upfront curative procedure. Liver transplantation achieved the best outcome, whether performed upfront (n = 791; 5-year survival, 79.0% [95% CI: 76.1-82.1]) or during subsequent steps (n = 2217; 5-year survival 80.9% [95% CI: 79.2-82.7]). Tumor ablation (n = 5306), open resection (n = 5171), and minimally-invasive resection (n = 1833) achieved 5-year survival rates of 53.8% (95% CI: 52.3-55.4), 54.1% (95% CI: 52.6-55.6), and 66.2% (95% CI: 63.7-68.7), respectively, with more patients with cirrhosis and subsequent procedures in the tumor ablation group. Patients with upfront transarterial (chemo)embolization (n = 10,247) and selective internal radiation therapy (n = 659) had 5-year survival rates of 31.3% (95% CI: 30.3-32.4) and 18.5% (95% CI: 15.2-22.5). CONCLUSION While HCC remains mostly diagnosed at an advanced stage associated with a poor prognosis, all the curative options provide 5-year survival rates above 50%.
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Affiliation(s)
- Christophe Cassinotto
- Department of Diagnostic and Interventional Radiology, Saint-Eloi Hospital, University Hospital of Montpellier, 34090 Montpellier, France; Institut Desbrest d'Epidémiologie et de Santé Publique, IDESP UMR UA11 INSERM, University Hospital of Montpellier, 34090 Montpellier, France.
| | - Erika Nogue
- Clinical Research and Epidemiology Unit, University Hospital of Montpellier, Montpellier University, 34090 Montpellier, France
| | - Quentin Durand
- Department of Diagnostic and Interventional Radiology, Saint-Eloi Hospital, University Hospital of Montpellier, 34090 Montpellier, France
| | - Fabrizio Panaro
- Department of Surgery/ Division of HBP Surgery and Transplantation, Saint-Eloi Hospital, University Hospital of Montpellier, 34090 Montpellier, France
| | - Eric Assenat
- Department of Oncology, Saint-Eloi Hospital, University Hospital of Montpellier, 34090 Montpellier, France
| | - Anthony Dohan
- Department of Radiology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Université Paris Cité, Faculté de Médecine, 75006 Paris, France
| | - Nicolas Malafaye
- Clinical Research and Epidemiology Unit, University Hospital of Montpellier, Montpellier University, 34090 Montpellier, France
| | - Boris Guiu
- Department of Diagnostic and Interventional Radiology, Saint-Eloi Hospital, University Hospital of Montpellier, 34090 Montpellier, France; Institut Desbrest d'Epidémiologie et de Santé Publique, IDESP UMR UA11 INSERM, University Hospital of Montpellier, 34090 Montpellier, France
| | - Nicolas Molinari
- Institut Desbrest d'Epidémiologie et de Santé Publique, IDESP UMR UA11 INSERM, University Hospital of Montpellier, 34090 Montpellier, France; Clinical Research and Epidemiology Unit, University Hospital of Montpellier, Montpellier University, 34090 Montpellier, France
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18
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Chen W, Hu S, Liu Z, Sun Y, Wu J, Shen S, Peng Z. Adjuvant anti-PD-1 antibody for hepatocellular carcinoma with high recurrence risks after hepatectomy. Hepatol Int 2023; 17:406-416. [PMID: 36645648 DOI: 10.1007/s12072-022-10478-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 12/27/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND PURPOSE The clinical role of postoperative adjuvant therapy in hepatocellular carcinoma (HCC) is still unclear. The purpose of our study was to explore the clinical value of postoperative adjuvant anti-programed cell death 1 antibody (PA-PD-1) on the prognosis of HCC patients with high relapse risks after surgery. PATIENTS AND METHODS Data of consecutive HCC patients with high recurrence risks treated with liver resection at our center during January 2019 and March 2021 were prospectively collected. Baseline differences were balanced between HCC patients with (PA-PD-1 group) or without PA-PD-1 (non-PD-1 group) after hepatectomy by propensity-score matching (PSM). Between these two groups, we compared overall survival (OS) and recurrence-free survival (RFS). Independent prognostic risk factors for OS and RFS were confirmed by Cox regression analysis, and subgroup analysis was also performed. RESULTS 47 pairs of patients with or without PD-1 treatment after hepatectomy were matched. After PSM, the 1-year and 2-year RFS was 58.4% and 44.1% in the PA-PD-1 group, and 34.0% and 21.3% in the non-PD-1 group (p = 0.008). The OS at 1 year and 2 years was 91.2% and 91.2% in the PA-PD-1 group, compared with 85.1% and 61.7% in the non-PD-1 group (p = 0.024). Multivariable analyses demonstrated that PA-PD-1 was an independent protective predictor associated with RFS and OS. Through subgroup analysis, we concluded that HCC patients with portal venous tumor thrombus (PVTT) or tumor size ≥ 5 cm significantly benefited from PA-PD-1 therapy in RFS and OS. CONCLUSIONS Adjuvant anti-PD-1 antibody can effectively improve the survival outcomes of HCC patients with high relapse risks after hepatectomy in this prospective observational study. This finding should be confirmed by results of the ongoing phase 3 randomized controlled trials.
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Affiliation(s)
- Wei Chen
- Center of Hepato-Pancreato- Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.,Department of Pancreaticobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Shuifang Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Zelong Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Yukun Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Jian Wu
- Center of Hepato-Pancreato- Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Shunli Shen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China. .,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. .,Cancer Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. .,Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
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Zhang X, Wang C, Zheng D, Liao Y, Wang X, Huang Z, Zhong Q. Radiomics nomogram based on multi-parametric magnetic resonance imaging for predicting early recurrence in small hepatocellular carcinoma after radiofrequency ablation. Front Oncol 2022; 12:1013770. [PMID: 36439458 PMCID: PMC9686343 DOI: 10.3389/fonc.2022.1013770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 10/24/2022] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND There are few studies on the application of radiomics in the risk prediction of early recurrence (ER) after radiofrequency ablation (RFA). This study evaluated the value of a multi-parametric magnetic resonance imaging (MRI, mpMRI)-based radiomics nomogram in predicting ER of small hepatocellular carcinoma (HCC) after RFA. MATERIALS AND METHODS A retrospective analysis was performed on 90 patients with small HCC who were treated with RFA. Patients were divided into two groups according to recurrence within 2 years: the ER group (n=38) and the non-ER group (n=52). Preoperative T1WI, T2WI, and contrast-enhanced MRI (CE-MRI) were used for radiomic analysis. Tumor segmentation was performed on the images and applied to extract 1316 radiomics features. The most predictive features were selected using analysis of variance + Mann-Whitney, Spearman's rank correlation test, random forest (importance), and least absolute shrinkage and selection operator analysis. Radiomics models based on each sequence or combined sequences were established using logistic regression analysis. A predictive nomogram was constructed based on the radiomics score (rad-score) and clinical predictors. The predictive efficiency of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC). Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomogram. RESULTS The radiomics model mpMRI, which is based on T1WI, T2WI, and CE-MRI sequences, showed the best predictive performance, with an AUC of 0.812 for the validation cohort. Combined with the clinical risk factors of albumin level, number of tumors, and rad-score of mpMRI, the AUC of the preoperative predictive nomogram in the training and validation cohorts were 0.869 and 0.812, respectively. DCA demonstrated that the combined nomogram is clinically useful. CONCLUSIONS The multi-parametric MRI-based radiomics nomogram has a high predictive value for ER of small HCC after RFA, which could be helpful for personalized risk stratification and further treatment decision-making for patients with small HCC.
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Affiliation(s)
- Xiaojuan Zhang
- Department of Radiology, Fujian Medical University Xiamen Humanity Hospital, Xiamen, China
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Chuandong Wang
- Department of Thyroid and Breast Surgery, Fujian Medical University Xiamen Humanity Hospital, Xiamen, China
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Dan Zheng
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Radiology, 900th Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Yuting Liao
- Institute of Precision Medicine, GE Healthcare, Shanghai, China
| | - Xiaoyang Wang
- Department of Radiology, 900th Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Zhifeng Huang
- Department of Radiology, 900th Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Qun Zhong
- Department of Radiology, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
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20
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Norcantharidin liposome emulsion hybrid delivery system enhances PD-1/PD-L1 immunotherapy by agonizing the non-canonical NF-κB pathway. Int J Pharm 2022; 628:122361. [DOI: 10.1016/j.ijpharm.2022.122361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/17/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022]
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Emadi SA, Ghasemzadeh Rahbardar M, Mehri S, Hosseinzadeh H. A review of therapeutic potentials of milk thistle ( Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2022; 25:1166-1176. [PMID: 36311193 PMCID: PMC9588316 DOI: 10.22038/ijbms.2022.63200.13961] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 06/21/2022] [Indexed: 11/06/2022]
Abstract
For more than 2000 years, Silybum marianum L. (milk thistle) has been used for treating different complications such as jaundice, hepatitis, and cancers. It has also been shown that silymarin, a flavonolignan extract of the plant, demonstrates chemopreventive effects against cancers. This patent review presents and discusses recent patents concerning the anticancer effects of S. marianum and silymarin. The data were gathered by searching an extensive literature review conducted in Google Scholar, PubMed, Scopus, Google Patent, Patent Scope, and US Patent. Milk thistle and silymarin have been used in a variety of medical, therapeutic, and pharmaceutical fields, according to a large number of documents and patents. Milk thistle and silymarin have been used as complementary treatments for cancers such as skin, prostate, and colorectal cancers, as well as hepatoprotective agents. Silymarin exerts a chemopreventive effect on reactivating cell death pathways by modulation of the antiapoptotic proteins and synergizing with agonists of death domain receptors. Based on the results of these patents, silymarin could be beneficial to oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics. Following the human propensity to use phytocompounds rather than medicines based on chemical constituents, special attention must be paid to tie the value of milk thistle and silymarin from basic science to clinical applications.
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Affiliation(s)
- Seyyed Amir Emadi
- Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahboobeh Ghasemzadeh Rahbardar
- Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soghra Mehri
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding authors: Soghra Mehri. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. ; Hossein Hosseinzadeh. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding authors: Soghra Mehri. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. ; Hossein Hosseinzadeh. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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22
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Tao L, Ding X, Yan L, Xu G, Zhang P, Ji A, Zhang L. CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption. MEDICAL ONCOLOGY (NORTHWOOD, LONDON, ENGLAND) 2022; 39:202. [PMID: 36175596 DOI: 10.1007/s12032-022-01808-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 07/22/2022] [Indexed: 12/24/2022]
Abstract
CD36 is emerging as a potential strategy for cancer treatment because of its function of regulating fatty acid intake. The purpose of this study was to clarify the molecular mechanism of CD36 in the progression of HCC. TCGA database was used to analyze the relationship of CD36 with HCC. The expression of CD36 in HCC clinical samples and cell lines was detected by qRT-PCR and western blot. Huh7 cells and HCCLM3 cells were transfected and treated into different group. CCK-8 and clone formation assay were used to detect the cell proliferation ability. Wound healing and transwell experiment were used to detect the metastatic ability. HCC xenografts were constructed in nude mice by subcutaneous injection of stably transfected Huh7 cells. The expression of CD36 in HCC was detected by immunohistochemistry (IHC). The contents of phospholipids and triglycerides in HCC cells were detected by ELISA. And the content of neutral lipids in HCC cells was detected by staining with BODIPY 493/503 and DAPI dye. Then transcriptional sequencing was used to determine the downstream mechanism of CD36 in HCC, and the differentially expressed genes (DEGs) were analyzed. CD36 was upregulated in HCC. Knockdown of CD36 could suppress the proliferation and metastasis of HCC in vitro and in vivo by regulating FAs intake in HCC. In addition, the expression of AKR1C2 was suppressed by sh-CD36, and which was also involved in the regulation of FAs intake. The molecular mechanism by which CD36 accelerated the progression of HCC was to promote the expression of AKR1C2 and thus enhance fatty acids (FAs) intake.
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Affiliation(s)
- Lide Tao
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225012, China
| | - Xiangmin Ding
- Department of Hepatobiliary Pancreatic Surgery, Subei People's Hospital of Jiangsu Province, Yangzhou, China
| | - Lele Yan
- Department of Hepatobiliary Pancreatic Surgery, Subei People's Hospital of Jiangsu Province, Yangzhou, China
| | - Guangcai Xu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225012, China
| | - Peijian Zhang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225012, China
| | - Anlai Ji
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225012, China
| | - Lihong Zhang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225012, China.
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23
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Han J, Wang B, Liu W, Wang S, Chen R, Chen M, Fu Z. Declining disease burden of HCC in the United States, 1992-2017: A population-based analysis. Hepatology 2022; 76:576-588. [PMID: 35073427 DOI: 10.1002/hep.32355] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/19/2022] [Accepted: 01/19/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND AIMS The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination. APPROACH AND RESULTS Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence-based mortality (IBM), and 1-year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute's Joinpoint Regression Program. Age-period-cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990-2019) as a likely validation set. Joinpoint and age-period-cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992-2011 and sharply decreased thereafter by -2.3% annually (95% CI: -3.5% to -1.1%). IBM peaked in 2013 (age-standardized mortality rate: 6.98 per 100,000 person-years) in the US population. IBM started to decrease significantly in 2013 by -3.2%/year (95% CI: -5.4% to -1.1% per year) after a continuous increase of 3.5% annually during 1993-2013. Overall, the 1-year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60-69 and born between 1952-1957 were found. CONCLUSIONS We found significantly decreased overall HCC-specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.
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Affiliation(s)
- Jianglong Han
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Bin Wang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wenmin Liu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shijie Wang
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ruyan Chen
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mingkai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhenming Fu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
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24
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Liu S, Sun L, Yao L, Zhu H, Diao Y, Wang M, Xing H, Lau WY, Guan M, Pawlik TM, Shen F, Xu M, Tong X, Yang T. Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. J Clin Med 2022; 11:5075. [PMID: 36079006 PMCID: PMC9456633 DOI: 10.3390/jcm11175075] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/18/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022] Open
Abstract
Background and Aim: Alpha-fetoprotein (AFP), a lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), is a protein that is induced by vitamin K deficiency or antagonist-II (PIVKA-II) that has been clinically used as a serum biomarker for early detection and diagnosis of hepatocellular carcinoma (HCC). Diagnostic performance of each serum biomarker alone, or their combinations for the detection of hepatitis C virus (HCV)-associated HCC were compared. Methods: Serum AFP, AFP-L3, and PIVKA-II levels were evaluated in patients with HCV-associated HCC, and those with chronic HCV infection without HCC (HCV-controls). The areas under the curve (AUC), sensitivity, and specificity were compared to identify the diagnostic performance of each serum HCC biomarker alone or in combination. Results: Overall, 172 HCV controls and 105 patients with HCV-associated HCC were enrolled. The AFP, AFP-L3, and PIVKA-II levels were significantly increased among patients with HCV-associated HCC when compared with HCV patients without HCC (p < 0.001). When these biomarkers were analyzed individually, PIVKA-II revealed the best predictive performance (AUC: PIVKA-II 0.90 vs. AFP 0.80 vs. AFP-L3 0.69, p < 0.001). In evaluating the combinations of any two biomarkers, the best predictive performance was found in PIVKA-II + AFP (0.93 vs. AFP + AFP-L3 0.78, p = 0.001; and PIVKA-II + AFP-L3 0.89, p < 0.001), which had no difference compared to the predictive performance of the combination of all three serum biomarkers (AFP + AFP-L3 + PIVKA-II 0.93, p = 0.277). Similar results were identified in the subgroups of patients with HCV-induced cirrhosis, and among patients with early-stage HCC defined by BCLC and TNM staging. Conclusions: The addition of the PIVKA-II test to routine AFP test maybe provide a more suitable biomarker approach to detect HCV-induced HCC in patients with HCV infection undergoing HCC surveillance.
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Affiliation(s)
- Siyu Liu
- Department of Laboratory Medicine, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
| | - Liyang Sun
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Lanqing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yongkang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Mingda Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China
| | - Mingcheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Min Xu
- Department of Interventional Radiology, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui 323050, China
| | - Xiangmin Tong
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
- Department of Laboratory, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’ s Hospital (People’ s Hospital of Hangzhou Medical College), No. 158, Shangtang Road, Hangzhou 310014, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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Gao G, Luan X. Diagnostic performance of clusterin in hepatocellular carcinoma: A meta-analysis. Int J Biol Markers 2022; 37:404-411. [PMID: 35645149 DOI: 10.1177/03936155221101206] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Introduction Clusterin (CLU) is a pleiotropic protein with numerous functions. It has recently attracted considerable attention owing to its association with cancer progression and metastasis. However, its role in hepatocellular carcinoma (HCC) has not been investigated. This meta-analysis is the first evaluation of the diagnostic performance of CLU in HCC. Methods Articles published in PubMed, EMBASE, Web of Science, Wanfang Data Knowledge Service Platform, and China Science and Technology Journal Database until January 2022 were searched. Studies that reported the usefulness of CLU for the differentiation of HCC and non-HCC (e.g., liver cirrhosis, chronic hepatitis, and other benign liver disease) patients were selected. Alpha-fetoprotein (AFP) was used as a positive control in this study. The sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were compared between CLU and AFP. Results Eight articles including 811 participants were included. The pooled sensitivity (95% confidence interval (CI)), specificity (95% CI), DOR (95% CI), and AUC (95% CI) were: 0.86 (0.78–0.91), 0.85 (0.75–0.91), 35 (13–94), and 0.92 (0.89–0.94) for CLU; 0.74 (0.67–0.81), 0.89 (0.79–0.94), 22 (8–61), and 0.87 (0.84–0.90) for AFP; 0.93 (0.88–0.96), 0.85 (0.68–0.94), 75 (21–262), and 0.95 (0.92–0.96) for CLU + AFP, respectively. Compared with AFP, CLU showed higher sensitivity, DOR, and AUC, as well as similar specificity. The combination of CLU and AFP resulted in higher sensitivity, DOR, and AUC. Conclusions Serum CLU is a better biomarker versus AFP for the diagnosis of HCC. The combination of CLU and AFP improved diagnostic performance.
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Affiliation(s)
- Ge Gao
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Xuke Luan
- IBM Dalian Global Delivery Company Limited, Shanghai, P.R. China
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Li G, He Y, Liu H, Liu D, Chen L, Luo Y, Chen L, Qi L, Wang Y, Wang Y, Wang Y, Zhan L, Zhang N, Zhu X, Song T, Guo H. DNAJC24 is a potential therapeutic target in hepatocellular carcinoma through affecting ammonia metabolism. Cell Death Dis 2022; 13:490. [PMID: 35606363 PMCID: PMC9127113 DOI: 10.1038/s41419-022-04953-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/04/2022] [Accepted: 05/13/2022] [Indexed: 12/14/2022]
Abstract
Evolutionarily conserved heat shock proteins are involved in the heat shock response of cells in response to changes in the external environment. In normal tissues, heat shock proteins can help cells survive in a rapidly changing environment. Likewise, in malignant tumors heat shock proteins may help tumor cells cope with external stresses as well as the stress of treatment. In this way they become accomplices of malignant tumors. Here we demonstrated for the first time that high expression of DNAJC24 (a heat shock protein) shortens survival in patients with HCC by immunohistochemical staining of 167 paired hepatocellular carcinomas and paraneoplastic tissues as well as data from public databases. In vitro experiments demonstrated that stimuli such as hypoxia, starvation and heat could upregulate DNAJC24 expression in HCC cells through transcriptional regulation of HSF2, and high expression of DNAJC24 in HCC cells could promote the proliferation and motility of HCC cells. In addition, we also verified that targeting DNAJC24 under normal culture conditions can affect the proliferation and autophagy of HCC cells by interfering with ammonia metabolism, thereby inhibiting the malignant progression of HCC. Overall, we suggested that DNAJC24 may become a new target for the treatment of HCC.
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Affiliation(s)
- Guangtao Li
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Yuchao He
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Hui Liu
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Dongming Liu
- grid.411918.40000 0004 1798 6427Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Lu Chen
- grid.411918.40000 0004 1798 6427Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Yi Luo
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Liwei Chen
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Lisha Qi
- grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China
| | - Yun Wang
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Yingying Wang
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Yu Wang
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Linlin Zhan
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Ning Zhang
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Xiaolin Zhu
- grid.411918.40000 0004 1798 6427Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Tianqiang Song
- grid.411918.40000 0004 1798 6427Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Hua Guo
- grid.411918.40000 0004 1798 6427Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China ,grid.411918.40000 0004 1798 6427National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
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Chen Z, Qi L, Fu H, Ma L. Long non-coding RNA X-inactive specific transcript suppresses the progression of hepatocellular carcinoma through microRNA-221-3p-targeted regulation of O6-methylguanine-DNA methyltransferase. Bioengineered 2022; 13:14013-14027. [PMID: 35723009 PMCID: PMC9275909 DOI: 10.1080/21655979.2022.2086382] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
MicroRNA-221-3p (miR-221-3p) is an important regulator involved in the progression and prognosis of various cancers. In this study, we aimed to investigate the diagnostic and prognostic value of miR-221-3p expression along with long non-coding RNA X–inactive specific transcript (XIST), which was identified as its upstream regulator in hepatocellular carcinoma (HCC) by bioinformatics analysis, and further validated by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Their expression was measured in tumor tissues and corresponding non-tumor tissues by quantitative real-time PCR (qRT-PCR), which revealed that XIST was weakly expressed in HCC cells and tumors, while miR-221-3p was overexpressed. Complete knockdown of XIST enhanced HCC cell proliferation and migration and inhibited apoptosis, as observed by MTT, transwell, and flow cytometry experiments, respectively. Animal studies validated that XIST knockdown induces tumor growth in vivo. In contrast, upregulation of XIST in HCC cells suppressed their proliferation and migration, stimulated apoptosis, and retarded the growth rate of tumors in vivo. These effects were partially reversed by upregulating miR-221-3p expression. Furthermore, we demonstrated that O6-methylguanine-DNA methyltransferase (MGMT) is a downstream target of miR-221-3p. It was weakly expressed in HCC cells and tumors and showed a negative correlation with miR-221-3p. Forced MGMT expression repressed proliferation and migration and enhanced apoptosis in HCC cells. Nevertheless, these anti-tumor effects induced by MGMT overexpression could be abolished by miR-221-3p upregulation. Collectively, our findings reveal that XIST blocks the development of HCC through miR-221-3p-targeted regulation of MGMT. This reveals a new mechanism involved in the development of HCC.
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Affiliation(s)
- Zushun Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Lunan Qi
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Hongyuan Fu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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28
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Yin J, Wen M, Cheng J, Hu L, Yang L, Chang X, Zhou Z, Li H, Liu Y, Li J. A Patient With Failed Liver Transplantation After the Use of PD-1 Blockade Combined With Lenvaxen. Front Med (Lausanne) 2022; 9:712466. [PMID: 35265635 PMCID: PMC8899006 DOI: 10.3389/fmed.2022.712466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/03/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with high extent of invasiveness. Its invasion process is closely related to complex tumor microenvironment and microvascular characteristics. Recently, immune combined targeted therapy has been applied to patients, combination therapy program with better effect needs to be explored. Atezolizumab combined Bevacizumab regimen in phase III clinical trial IMbrave150 was approved by U.S. Federal Drug Administration (FDA) for HCC treatment. This program is mostly used for liver malignant tumors have failed other treatments. Patients in terminal stage, overall curative has an unsatisfactory effect, survival time of patients is limited. Therefore, seeking best plan for combined treatment to improve patient's life quality and survival rate are still one of the most important clinical difficulties. This report describes a 37-year-old male who suffered from HCC repeatedly relapsed after hepatectomy. The patient received transcatheter arterial chemoembolization (TACE), microwave ablation (MWA), targeted therapy, and other combined treatments, all showed poor treatment effects. He received liver transplantation (LT) after receiving PD-1 blockade combined targeted therapy, eventually died due to severe immune rejection. It's first case of an allogeneic liver transplantation patient who received PD-1 blockade and Lenvaxen combined therapy. PD-1 blockade treatment and clinical observations of this case were summarized.
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Affiliation(s)
- Jun Yin
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China
| | - Meng Wen
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China
| | - Jun Cheng
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China
| | - Lifen Hu
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China
| | - Li Yang
- Department of Basic Medical Sciences, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China
| | - Xiao Chang
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China
| | - Zhongsong Zhou
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hongbin Li
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yan Liu
- Department of Basic Medical Sciences, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China
| | - Jiabin Li
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, China.,Department of Infectious Diseases, The Chaohu Hospital of Anhui Medical University, Hefei, China
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Li Y, Zhang J, Zhang K, Chen Y, Wang W, Chen H, Zou Z, Li Y, Dai M. Scutellaria barbata Inhibits Hepatocellular Carcinoma Tumorigenicity by Inducing Ferroptosis of Hepatocellular Carcinoma Cells. Front Oncol 2022; 12:693395. [PMID: 35321425 PMCID: PMC8936062 DOI: 10.3389/fonc.2022.693395] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Ferroptosis is caused by accumulation of iron-dependent lipid peroxidation, which is characterized by reduction in cell volume and increase in mitochondrial membrane density. Studies have shown that ferroptosis contributes to the development and progression of numerous major diseases, including hepatocellular carcinoma (HCC). As a unique biomedical resource, Traditional Chinese Medicine (TCM) has been widely used in the treatment of HCC. In this present study, Scutellaria barbata was used to treat HCC cells in vitro, and the results revealed that S. barbata suppressed HCC cell growth through inducing ferroptosis. Next, the exploration of the molecular mechanism on how S. barbata induced ferroptosis in HCC cells suggested that S. barbata may induce ferroptosis by promoting iron perioxidation and lipid ROS metabolism. Finally, S. barbata also inhibited HCC tumorigenicity in vivo by inducing ferroptosis of HCC cells. These results provided theoretical basis for explaining the mechanism of TCM treatment for HCC and offered therapeutic opportunities for HCC patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Min Dai
- *Correspondence: Yongwei Li, ; Min Dai,
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30
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Xu W, Cheng Y, Guo Y, Yao W, Qian H. Targeting tumor associated macrophages in hepatocellular carcinoma. Biochem Pharmacol 2022; 199:114990. [PMID: 35288152 DOI: 10.1016/j.bcp.2022.114990] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/02/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022]
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Zhou X, Zhang T, Sun Y, Li C, Ding X, Zhu Y, Li L, Fan Z. Systematic Review and Meta-analysis: Association of Aspirin With Incidence of Hepatocellular Carcinoma. Front Pharmacol 2022; 13:764854. [PMID: 35300300 PMCID: PMC8921872 DOI: 10.3389/fphar.2022.764854] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 01/31/2022] [Indexed: 12/24/2022] Open
Abstract
Aim: To explore the relationship between the use of aspirin and the incidence of hepatocellular carcinoma (HCC). Methods: MEDLINE, EMBASE, Web of Science and Cochrane CENTRAL databases were searched systematically from the earliest available date to 13 March 2020. The primary outcome was incidence of HCC, and the secondary outcomes were recurrence and mortality of HCC. The results were expressed as the Hazard Ratio (HR) and 95% confidence interval (CI). Based on the heterogeneity evaluated with the I 2 statistic, a meta-analysis was performed using either a random- or fixed-effects model. Results: A total of sixteen articles (2781100 participants) were included. There was lower incidence of HCC in aspirin users than those in non-aspirin users (HR, 0.56; 95% CI, 0.46-0.69; p < 0.001). Subgroup analysis further showed that the incidence of liver cancer in patients with alcoholic cirrhosis (HR, 0.14; 95% CI, 0.09-0.22; p < 0.001) and virus hepatitis (HR, 0.68; 95% CI, 0.62-0.74; p < 0.001) who use aspirin was lower than that of patients who do not use aspirin. In addition, aspirin was found to associate with decreased risk of HCC mortality (HR, 0.71; 95% CI, 0.65-0.78; p < 0.001), not HCC recurrence (HR, 0.52; 95% CI, 0.15-1.76; p = 0.291). Conclusions: Aspirin use is significantly associated with the low incidence rate of liver cancer.
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Affiliation(s)
- Xueliang Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tengfei Zhang
- Cancer Centre, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yali Sun
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
| | - Chunwei Li
- Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, China
| | - Xianfei Ding
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
| | - Yanhui Zhu
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
| | - Lifeng Li
- Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, China
| | - Zhirui Fan
- Integrated Traditional and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Tayob N, Lok ASF, Feng Z. A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers. Stat Med 2022; 41:2338-2353. [PMID: 35199349 DOI: 10.1002/sim.9358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 02/01/2022] [Accepted: 02/03/2022] [Indexed: 11/11/2022]
Abstract
The early detection of hepatocellular carcinoma (HCC) is critical to improving outcomes since advanced HCC has limited treatment options. Current guidelines recommend HCC ultrasound surveillance every 6 months in high-risk patients however the sensitivity for detecting early stage HCC in clinical practice is poor. Blood-based biomarkers are a promising direction since they are more easily standardized and less resource intensive. Combining of multiple biomarkers is more likely to achieve the sensitivity required for a clinically useful screening algorithm and the longitudinal trajectory of biomarkers contains valuable information that should be utilized. We propose a multivariate parametric empirical Bayes (mPEB) screening approach that defines personalized thresholds for each patient at each screening visit to identify significant deviations that trigger additional testing with more sensitive imaging. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial provides a valuable source of data to study HCC screening algorithms. We study the performance of the mPEB algorithm applied to serum α -fetoprotein, a widely used HCC surveillance biomarker, and des- γ carboxy prothrombin, an HCC risk biomarker that is FDA approved but not used in practice in the United States. Using cross-validation, we found that the mPEB algorithm demonstrated moderate but improved sensitivity compared to alternative screening approaches. Future research will validate the clinical utility of the approach in larger cohort studies with additional biomarkers.
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Affiliation(s)
- Nabihah Tayob
- Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Anna S F Lok
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Ziding Feng
- Biostatistics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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33
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Lu L, Zhuang Z, Fan M, Liu B, Yang Y, Huang J, Da X, Mo J, Li Q, Lu H. Green formulation of Ag nanoparticles by Hibiscus rosa-sinensis: Introducing a navel chemotherapeutic drug for the treatment of liver cancer. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2021.103602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Forjaz G, Howlader N, Scoppa S, Johnson CJ, Mariotto AB. Impact of including second and later cancers in cause-specific survival estimates using population-based registry data. Cancer 2022; 128:547-557. [PMID: 34623641 PMCID: PMC8776580 DOI: 10.1002/cncr.33940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/15/2021] [Accepted: 09/07/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Second or later primary cancers account for approximately 20% of incident cases in the United States. Currently, cause-specific survival (CSS) analyses exclude these cancers because the cause of death (COD) classification algorithm was available only for first cancers. The authors added rules for later cancers to the Surveillance, Epidemiology, and End Results cause-specific death classification algorithm and evaluated CSS to include individuals with prior tumors. METHODS The authors constructed 2 cohorts: 1) the first ever primary cohort, including patients whose first cancer was diagnosed during 2000 through 2016) and 2) the earliest matching primary cohort, including patients with any cancer who matched the selection criteria irrespective of whether it was the first or a later cancer diagnosed during 2000 through 2016. The cohorts' CSS estimates were compared using follow-up through December 31, 2017. The new rules were used in the second cohort for patients whose first cancers during 2000 through 2016 were their second or later cancers. RESULTS Overall, there were no statistically significant differences in CSS estimates between the 2 cohorts. Estimates were similar by age, stage, race, and time since diagnosis, except for patients with leukemia and those aged 65 to 74 years (3.4 percentage point absolute difference). CONCLUSIONS The absolute difference in CSS estimates for the first cancer ever cohort versus earliest of any cancers cohort in the study period was small for most cancer types. As the number of newly diagnosed patients with prior cancers increases, the algorithm will make CSS more inclusive and enable estimating survival for a group of patients with cancer for whom life tables are not available or life tables are available but do not capture other-cause mortality appropriately.
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Affiliation(s)
- Gonçalo Forjaz
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA,Azores Cancer Registry, Azores Oncological Centre, Portugal,Corresponding author: Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Room 4E568, Rockville, MD 20850, USA. (G. Forjaz)
| | - Nadia Howlader
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
| | - Steve Scoppa
- Information Management Services, Inc., Calverton, MD, USA
| | | | - Angela B. Mariotto
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
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35
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Martin D, Maeder Y, Kobayashi K, Schneider M, Koerfer J, Melloul E, Halkic N, Hübner M, Demartines N, Becce F, Uldry E. Association between CT-Based Preoperative Sarcopenia and Outcomes in Patients That Underwent Liver Resections. Cancers (Basel) 2022; 14:cancers14010261. [PMID: 35008425 PMCID: PMC8750804 DOI: 10.3390/cancers14010261] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Cancer cachexia often includes sarcopenia, which is characterized by a progressive, generalized loss of skeletal muscle mass and strength, combined with fatty infiltration into the muscle. Sarcopenia has been considered a patient-specific imaging biomarker for predicting outcomes after cancer surgery. The present study aimed to evaluate whether preoperative sarcopenia was associated with postoperative outcomes and survival in patients that underwent liver resections. Sarcopenia, assessed by preoperative CT imaging, was present in two-thirds of patients. Independent risk factors for sarcopenia were age, male sex, ASA score ≥ 3, and malignancies. Based on CT assessment alone, sarcopenia had no impact on clinical outcomes or overall survival after hepatectomy. Abstract This retrospective observational study aimed to evaluate whether preoperative sarcopenia, assessed by CT imaging, was associated with postoperative clinical outcomes and overall survival in patients that underwent liver resections. Patients operated on between January 2014 and February 2020 were included. The skeletal muscle index (SMI) was measured at the level of the third lumbar vertebra on preoperative CT scans. Preoperative sarcopenia was defined based on pre-established SMI cut-off values. The outcomes were postoperative morbidity, length of hospital stay (LOS), and overall survival. Among 355 patients, 212 (59.7%) had preoperative sarcopenia. Patients with sarcopenia were significantly older (63.5 years) and had significantly lower BMIs (23.9 kg/m2) than patients without sarcopenia (59.3 years, p < 0.01, and 27.7 kg/m2, p < 0.01, respectively). There was no difference in LOS (8 vs. 8 days, p = 0.75), and the major complication rates were comparable between the two groups (11.2% vs. 11.3%, p = 1.00). The median overall survival times were comparable between patients with sarcopenia and those without sarcopenia (15 vs. 16 months, p = 0.87). Based on CT assessment alone, preoperative sarcopenia appeared to have no impact on postoperative clinical outcomes or overall survival in patients that underwent liver resections. Future efforts should also consider muscle strength and physical performance, in addition to imaging, for preoperative risk stratification.
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Affiliation(s)
- David Martin
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
| | - Yaël Maeder
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (Y.M.); (J.K.); (F.B.)
| | - Kosuke Kobayashi
- Hepato-Pancreatico-Biliary Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8654, Japan;
| | - Michael Schneider
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
| | - Joachim Koerfer
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (Y.M.); (J.K.); (F.B.)
| | - Emmanuel Melloul
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
| | - Nermin Halkic
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
- Correspondence: ; Tel.: +41-21-314-24-00
| | - Fabio Becce
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (Y.M.); (J.K.); (F.B.)
| | - Emilie Uldry
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland; (D.M.); (M.S.); (E.M.); (N.H.); (M.H.); (E.U.)
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Sümbül Taner A, Beşen AA. Recent advances in medical treatment of hepatocellular cancer. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA, VOLUME 3 2022:365-375. [DOI: 10.1016/b978-0-323-99283-1.00004-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Fan Z, Wu M, Tang Z, He A, Liu F, Liang W, Wang Z, Yang D. Predictive Value of Platelet-Related Measures in Patients with Hepatocellular Carcinoma. Technol Cancer Res Treat 2022; 21:15330338211064414. [PMID: 35225081 PMCID: PMC8891878 DOI: 10.1177/15330338211064414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Increasing numbers of studies reported platelet (PLT)- related measures could play a creative role in many malignancies, while the prognostic impact of these measures in hepatocellular carcinoma (HCC) remains limited and controversial. It is worth exploring the predictive value of PLT-related measures in HCC. Methods: A total of 279 HCC patients with hepatectomy were analyzed in the retrospective cohort study. The optimal cut-off points of these PLT-related indices were obtained by the receiver operating characteristic (ROC) curve. The associations of these indices with clinical characteristics and overall survival (OS) were evaluated by Kaplan–Meier curves and Cox proportional hazards models. Results: High PLT count and low prognostic nutritional index (low-PNI) were significantly associated with larger tumor size. The low gamma-glutamyl transpeptidase-to-platelet ratio (low-GPR) group was inclined to more hepatitis infections. Survival curves indicated that preoperative high-PLT, low-GPR, and low-PNI had a worse prognosis after surgery in the cohort. In addition, PLT≥220 × 109/L (HR, 2.274; 95% CI, 1.061-4.876; P = .035), PNI≥51.9 (HR, 0.503; 95% CI, 0.265-0.954; P = .035), and GPR≥0.2 (HR, 0.432; 95% CI, 0.204-0.912; P = .028) were identified as independent prognostic factors for survival outcomes in the multivariable analysis. Conclusion: High-PLT, low-GPR, and low-PNI as the preoperative predictors were associated with poor OS in HCC patients with hepatectomy. Our data reveal that they could be simple, easily obtained, and effective predictors for evaluation of survival outcomes in patients.
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Affiliation(s)
- Zhijia Fan
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Mengmeng Wu
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Zihui Tang
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Anfang He
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Fuchen Liu
- 535219Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei Liang
- The Second People's Hospital of Lianyungang City, Jiangsu Province, China
| | - Zhicheng Wang
- Huashan Hospital, 159397Fudan University, Shanghai, China
| | - Dongqin Yang
- Huashan Hospital, 159397Fudan University, Shanghai, China
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LR-M Observations on Contrast-Enhanced Ultrasound: Detection of Hepatocellular Carcinoma Using Additional Features in Comparison with Current LI-RADS Criteria. AJR Am J Roentgenol 2021; 219:76-85. [PMID: 34910538 DOI: 10.2214/ajr.21.26837] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background: Contrast-enhanced ultrasound (CEUS) LI-RADS assigns category LR-M for observations that are definitely or probably malignant but that are not specific on imaging for hepatocellular carcinoma (HCC). A high percentage of LR-M observations represent HCC. Objective: To retrospectively evaluate the utility of additional features, beyond conventional LI-RADS major features, for detecting HCC among LR-M observations on CEUS. Methods: This retrospective study included 174 patients (145 men, 29 women; mean age, 53 years) at high-risk for HCC who underwent CEUS from August 2014 to June 2016, demonstrating an LR-M observation using CEUS LI-RADS version 2017. Two radiologists independently assessed CEUS images for major features and four additional features (chaotic vessels, peripheral circular artery, clear boundary of the tumor enhancement, clear boundary of the intratumoral nonenhanced area). Diagnostic performance was assessed of four proposed criteria for the detection of HCC among LR-M observations. The impact on HCC detection of criteria based on the additional findings was further explored. Histology or composite imaging and clinical follow-up served as reference standard. Results: The 174 LR-M observations included 142 HCCs and 32 non-HCCs (20 intrahepatic cholangiocarcinomas, 5 combined hepatocellular-cholangiocarcinomas, 7 benign lesions). Interreader agreement of the additional features, expressed as kappa, ranged from 0.65 to 0.88. Two of the additional features exhibited PPV ≥95.0% for HCC: chaotic vessels (95.0%) and peripheral circular arteries (98.1%). The presence of either of these two additional features achieved sensitivity of 50.7%, specificity of 90.6%, PPV of 96.0%, and NPV of 29.3% for HCC. Three other explored criteria incorporating variations of major LI-RADS features, but not the additional features, had sensitivities of 55.6%-96.5%, specificities of 49.6%-68.8%, PPVs of 87.8%-90.6%, and NPVs of 25.0%-75.0%. Criteria using additional features recategorized 75 of 174 LR-M observations as LR-5, of which 72 were HCC. Conclusion: The presence of chaotic vessels and/or peripheral circular artery had high specificity and PPV for HCC among LR-M observations. Other explored criteria based on major features did not achieve higher specificity or PPV. Clinical Impact: Clinical adoption of the additional CEUS features could help establish the diagnosis of HCC noninvasively and avoid the need for biopsy of LR-M observations.
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Elrefaey Hasan BM, Abd ElHamid HAE, Khater NH, ElGendy W, Abdelrahman AS. Role of DWI in evaluation of HCC after radiofrequency ablation compared to dynamic MRI using MRI (3 T). THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00647-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The purpose of this study was to investigate the diagnostic performance of diffusion weight imaging (DWI), apparent diffusion coefficient (ADC) map, normalized ADC liver, and normalized ADC spleen compared to the dynamic contrast-enhanced MRI (DCE-MRI) in the evaluation of residual hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) using 3 T (T) magnetic resonance imaging (MRI).
Results
A prospective study was performed on 40 patients with radiofrequency-ablated HCC, and 15 (37.5%) patients had viable lesion post-RFA, while 25 (62.5%) had non-viable lesions. DCE-MRI had a sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively, compared to DWI which had a sensitivity, specificity, and accuracy of 80%, 88%, and 85%, respectively, for identifying post-RFA viable HCC. The sensitivity, specificity, and accuracy of ADC at a cutoff value of 1.01 × 10−3 mm2/s were 80%, 100%, and 97.1%, respectively. The optimal cutoff value of normalized ADC liver was 0.81 with a sensitivity of 73.3%, specificity of 96%, and accuracy of 92.8%. The sensitivity, specificity, and accuracy of normalized ADC spleen at a cutoff value of 1.22 were 80%, 92%, and 91.1%, respectively.
Conclusions
DWI-MRI is a reliable technique for assessing HCC after radiofrequency ablation. DWI-MRI with ADC may be used as an alternate sequence for assessing radiofrequency-ablated lesions in individuals who have a contraindication to the contrast media, and the normalized ADC value may be of additional benefit.
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Ibrahim YF, Refaie MM, Kamel MY, Ahmed SM, Moussa RA, Bayoumi AM, Ibrahim MA. Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid-induced hepatic pre-neoplastic lesions in rats. Hum Exp Toxicol 2021; 40:S788-S803. [PMID: 34794354 DOI: 10.1177/09603271211056331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
CONCLUSION IL-1β mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.
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Affiliation(s)
- Yasmine F Ibrahim
- Department of Pharmacology, Faculty of Medicine, 68877Minia University, Minia, Egypt
| | - Marwa Mm Refaie
- Department of Pharmacology, Faculty of Medicine, 68877Minia University, Minia, Egypt
| | - Maha Y Kamel
- Department of Pharmacology, Faculty of Medicine, 68877Minia University, Minia, Egypt
| | - Sara M Ahmed
- Department of Pharmacology, Faculty of Medicine, 68877Minia University, Minia, Egypt
| | - Rabab A Moussa
- Department of Pathology, Faculty of Medicine, 68877Minia University, Minia, Egypt
| | - Asmaa Ma Bayoumi
- Department of Biochemistry, Faculty of Pharmacy, 68877Minia University, Minia, Egypt.,Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Mohamed A Ibrahim
- Department of Pharmacology, Faculty of Medicine, 68877Minia University, Minia, Egypt
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The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment. Int J Mol Sci 2021; 22:ijms221910630. [PMID: 34638971 PMCID: PMC8508708 DOI: 10.3390/ijms221910630] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/27/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene expression. Through these processes, lncRNAs can target microRNAs (miRNAs) to form lncRNA and miRNA networks, which regulate cancer cell proliferation, metastasis, drug resistance, and the tumor microenvironment. Here, we summarize the multifaceted functions of lncRNA and miRNA networks in the pathogenesis of HCC, the potential use of diagnostic or prognostic biomarkers, and novel therapeutic targets in HCC. This review also highlights the regulatory effects of lncRNA and miRNA networks in the tumor microenvironment of HCC.
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Liao R, Zhang D, Li X, Ma J, Yu J, Yang C, Xiong H, Zhou B, Huang X, Tang Z. A Preliminary Study on the Diagnostic Efficacy of Proton Magnetic Resonance Spectroscopy at 3.0T in Rabbit With VX2 Liver Tumor. Technol Cancer Res Treat 2021; 20:15330338211036852. [PMID: 34372732 PMCID: PMC8361547 DOI: 10.1177/15330338211036852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background: To investigate the diagnostic efficacy of choline (Cho) value of magnetic resonance spectroscopy (MRS) in rabbit with VX2 liver tumor via comparative and quantitative analysis with the choline compounds concentration measured by enzyme linked immunosorbent assay (ELISA). Methods: MRS was performed on normal liver and VX2 tumor. The Cho value of VX2 tumor was compared with that of normal liver. Tissues were harvested for ELISA to detect the concentrations of acetylcholine (ACh), glycophorophosphygholine (GPC) and phosphochorine (PC). The diagnostic performance of Cho value and concentrations of choline compounds were assessed by receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were discussed by the maximum Youden’s index. Results: The concentration of ACh was obviously higher than that of GPC and PC both in VX2 tumor and normal liver (P < 0.01). Furthermore, the concentration differences among ACh, GPC and PG were the third power of 10. Both the ACh concentration and Cho value of MRS in VX2 tumor were significantly higher than those in normal liver (P < 0.01). The AUC of ACh in VX2 tumor was 0.883, when the cutoff value was 7259000, the sensitivity and specificity of the diagnosis of liver cancer were 94.4% and 77.8%, respectively. The AUC of Cho in VX2 tumor was 0.807, when the cutoff value was 28.35, the sensitivity and specificity of the diagnosis of liver cancer were 83.3% and 77.8%, respectively. Conclusion: The change of Cho value in MRS between liver cancer and normal liver was consistent with the changes of concentrations of choline compounds measured by ELISA, especially the change of ACh concentration. The diagnostic efficiency of Cho value and that of choline compounds concentration in liver cancer were extremely similar, with the AUC more than 0.8. We conclude that MRS may be applied as an important, non-invasive biomarker for the diagnosis of liver cancer.
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Affiliation(s)
- Ruikun Liao
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Dan Zhang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Xiaojiao Li
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Jiang Ma
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Jiayi Yu
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Chao Yang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Hua Xiong
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Bi Zhou
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Xianlong Huang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Zhuoyue Tang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
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Zhu S, Cao S, Yang W, Che J, Li D, Pei R, Ding Y. The Maturation of Tumor Suppressor miR-497 in Hepatocellular Carcinoma is Inhibited by Oncogenic circRNA SCARB1. Cancer Manag Res 2021; 13:5751-5759. [PMID: 34305409 PMCID: PMC8292958 DOI: 10.2147/cmar.s304125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 06/11/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction Circular RNA (CircRNA) SCARB1 plays an oncogenic role in renal cell carcinoma, while its role in other cancers is unclear. The aim of this study was to explore the role of circRNA SCARB1 in hepatocellular carcinoma (HCC). Methods The expression of circRNA SCARB1, mature miR-497 and miR-497 precursor in HCC and paired non-tumor tissues from 64 HCC patients were analyzed by RT-qPCR. CircRNA SCARB1 was overexpressed in HCC cells, followed by the measurement of the expression levels of both mature miR-497 and miR-497 precursor to evaluate the effects of overexpression of circRNA SCARB1 on the maturation of miR-497. The effects of circRNA SCARB1 and miR-497 on the proliferation and migration of HCC cells were assessed by CCK-8 assay and Transwell assay, respectively. Results We found that circRNA SCARB1 was upregulated in HCC. In addition, mature miR-497 and miR-497 were downregulated in HCC. Correlation analysis showed that circRNA SCARB1 was inversely correlated with mature miR-497 but not miR-497 precursor. Consistently, in HCC cells, downregulated mature miR-497, but not miR-497 precursor, was observed in HCC cells transfected with circRNA SCARB1 expression vector. Analysis of cellular behaviors showed that overexpression of circRNA SCARB1 increased the proliferation and migration of HCC cells, while overexpression of miR-497 decreased cell proliferation and migration. Moreover, overexpression of miR-497 reduced the effects of overexpression of circRNA SCARB1. Discussion Therefore, circRNA SCARB1 is upregulated in HCC and promotes HCC cell proliferation and migration by suppressing the maturation of miR-497.
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Affiliation(s)
- Shuo Zhu
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Shengya Cao
- Department of Clinical Laboratory, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Weibin Yang
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Jinhui Che
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Deqiang Li
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Ruifeng Pei
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
| | - Yiren Ding
- Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China
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Zeng C, Tang Y, Jiang Y, Zuo Z, Tao H. Long noncoding RNAs as biomarkers for the diagnosis of hepatocellular carcinoma: A meta-analysis. Pathol Res Pract 2021; 224:153546. [PMID: 34332221 DOI: 10.1016/j.prp.2021.153546] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are often aberrantly expressed in hepatocellular carcinoma (HCC). The role of lncRNAs in the diagnosis of HCC has attracted increasing attention. Hence, we performed a meta-analysis based on current studies to assess the diagnostic value of lncRNAs for HCC. METHODS A systematic search was performed using PubMed, Web of Science, and Embase databases for relevant studies. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). A fixed-effect model was used if the value of I2 statistics < 50%; otherwise, a bivariate random effects model was applied (I2 ≥ 50%). In addition, subgroup analysis and meta-regression analysis were conducted to explore the sources of heterogeneity. Statistical analyses were based on Meta-Disc statistical software (Version 1.4) and STATA software (Version 15.1). RESULTS A total of 52 studies in 20 related articles were selected for this meta-analysis, including 4930 patients and 4614 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.85 [95% confidence interval (CI) 0.82-0.88], 0.76 (95% CI 0.73-0.80), 3.6 (95% CI 3.1-4.2), 0.19 (95% CI 0.16-0.24), 19 (95% CI 14-26), and 0.88 (95% CI 0.85-0.91), respectively. The publication bias was evaluated by the Deek's funnel plot in our meta-analysis. CONCLUSIONS LncRNAs can serve as feasible HCC diagnostic biomarkers. However, further studies are necessary to confirm its diagnostic and clinical value.
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Affiliation(s)
- Chuyi Zeng
- Department of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yan Tang
- Department of Clinical Laboratory, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, China
| | - Yao Jiang
- Department of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zhihua Zuo
- Department of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hualin Tao
- Department of Clinical Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
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Dian MJ, Li J, Zhang XL, Li ZJ, Zhou Y, Zhou W, Zhong QL, Pang WQ, Lin XL, Liu T, Liu YA, Li YL, Han LX, Zhao WT, Jia JS, Xiao SJ, Xiao D, Xia JW, Hao WC. MST4 negatively regulates the EMT, invasion and metastasis of HCC cells by inactivating PI3K/AKT/Snail1 axis. J Cancer 2021; 12:4463-4477. [PMID: 34149910 PMCID: PMC8210547 DOI: 10.7150/jca.60008] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/08/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a poor prognosis due to the high incidence of invasion and metastasis-related progression. However, the underlying mechanism remains elusive, and valuable biomarkers for predicting invasion, metastasis, and poor prognosis of HCC patients are still lacking. Methods: Immunohistochemistry (IHC) was performed on HCC tissues (n = 325), and the correlations between MST4 expression of the clinical HCC tissues, the clinicopathologic features, and survival were further evaluated. The effects of MST4 on HCC cell migratory and invasive properties in vitro were evaluated by Transwell and Boyden assays. The intrahepatic metastasis mouse model was established to evaluate the HCC metastasis in vivo. The PI3K inhibitor, LY294002, and a specific siRNA against Snail1 were used to investigate the roles of PI3K/AKT pathway and Snail1 in MST4-regulated EMT, migration, and invasion of HCC cells, respectively. Results: In this study, by comprehensively analyzing our clinical data, we discovered that low MST4 expression is highly associated with the advanced progression of HCC and serves as a prognostic biomarker for HCC patients of clinical-stage III-IV. Functional studies indicate that MST4 inactivation induces epithelial-to-mesenchymal transition (EMT) of HCC cells, promotes their migratory and invasive potential in vitro, and facilitates their intrahepatic metastasis in vivo, whereas MST4 overexpression exhibits the opposite phenotypes. Mechanistically, MST4 inactivation elevates the expression and nuclear translocation of Snail1, a key EMT transcription factor (EMT-TF), through the PI3K/AKT signaling pathway, thus inducing the EMT phenotype of HCC cells, and enhancing their invasive and metastatic potential. Moreover, a negative correlation between MST4 and p-AKT, Snail1, and Ki67 and a positive correlation between MST4 and E-cadherin were determined in clinical HCC samples. Conclusions: Our findings indicate that MST4 suppresses EMT, invasion, and metastasis of HCC cells by modulating the PI3K/AKT/Snail1 axis, suggesting that MST4 may be a potential prognostic biomarker for aggressive and metastatic HCC.
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Affiliation(s)
- Mei-Juan Dian
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.,Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Jing Li
- Radiotherapy Center, the First People's Hospital of Chenzhou, Xiangnan University, Chenzhou 423000, China
| | - Xiao-Ling Zhang
- Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China
| | - Zi-Jian Li
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ying Zhou
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wei Zhou
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Qiu-Ling Zhong
- State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wen-Qian Pang
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiao-Lin Lin
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Tao Liu
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yi-An Liu
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yong-Long Li
- Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Liu-Xin Han
- The third people's hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China
| | - Wen-Tao Zhao
- Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming 650118, China
| | - Jun-Shuang Jia
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Sheng-Jun Xiao
- Department of Pathology, the Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China
| | - Dong Xiao
- Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.,Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
| | - Jia-Wei Xia
- The third people's hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China
| | - Wei-Chao Hao
- Department of Oncology, The First Affiliation Hospital of Guangdong Pharmaceutical University, Guangzhou 510062, China
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Wen N, Liu F, Zhang H, Lu J, Li B, Cheng N. Laparoscopic liver resection for hepatocellular carcinoma presents less respiratory complications compared with open procedure: A propensity score analysis in the elderly. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2675-2681. [PMID: 34059378 DOI: 10.1016/j.ejso.2021.04.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 04/08/2021] [Accepted: 04/26/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Resection is still the most efficacious treatment to hepatocellular carcinoma (HCC), among which laparoscopic liver resection (LLR) have controversial effects against conventional open procedure (OLR). With a predictable aging tendency of population worldwide, conventional surgical procedures need to be modified to better accommodate elderly patients. Here, we designed a retrospective study based on propensity score analysis, aiming to compare the efficacy of OLR and LLR in patients over 65 years. METHODS We retrospectively analyzed patients with an age over 65 who underwent liver resection between January 2015 and September 2018. Patients were divided into the LLR group and OLR group. Short-term and long-term outcomes were compared before and after 1:1 propensity score matching. RESULTS Among 240 enrolled patients, 142 were matched with comparable baseline (71 each group). In the matched cohort, LLR group presented with shorter postoperative hospital stay (median 7 vs 6 days, p = 0.003) and fewer respiratory complications (19.7% vs. 7.0%, p = 0.049), especially pleural effusion (15.5% vs. 2.8%, p = 0.020). Meanwhile, LLR had comparable overall hospital cost (6142 vs. 6243 USD, p = 0.977) compared with OLR. The overall survival (OS) and disease-free survival (DFS) did not differ in the two groups. CONCLUSIONS Our study showed that laparoscopic liver resection for HCC in the older age groups is associated with shorter postoperative hospital stay and comparable hospital cost compared with open procedure, which could be attributable to less respiratory complications. We recommend that laparoscopy be taken as a priority option for elderly patients with resectable HCC.
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Affiliation(s)
- Ningyuan Wen
- Department of Biliary Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China
| | - Fei Liu
- Department of Liver Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China
| | - Haili Zhang
- Department of Liver Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China
| | - Jiong Lu
- Department of Biliary Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China
| | - Bei Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China.
| | - Nansheng Cheng
- Department of Biliary Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan Province, PR China.
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Wen L, Weng S, Yan C, Ye R, Zhu Y, Zhou L, Gao L, Li Y. A Radiomics Nomogram for Preoperative Prediction of Early Recurrence of Small Hepatocellular Carcinoma After Surgical Resection or Radiofrequency Ablation. Front Oncol 2021; 11:657039. [PMID: 34026632 PMCID: PMC8139248 DOI: 10.3389/fonc.2021.657039] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
Background Patients with small hepatocellular carcinoma (HCC) (3 cm) still have a poor prognosis. The purpose of this study was to develop a radiomics nomogram to preoperatively predict early recurrence (ER) (2 years) of small HCC. Methods The study population included 111 patients with small HCC who underwent surgical resection (SR) or radiofrequency ablation (RFA) between September 2015 and September 2018 and were followed for at least 2 years. Radiomic features were extracted from the entire tumor by using the MaZda software. The least absolute shrinkage and selection operator (LASS0) method was applied for feature selection, and radiomics signature construction. A rad-score was then calculated. Multivariable logistic regression analysis was used to establish a prediction model including independent clinical risk factors, radiologic features and rad-score, which was ultimately presented as a radiomics nomogram. The predictive ability of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve and internal validation was performed via bootstrap resampling and 5-fold cross-validation method. Results A total of 53 (53/111, 47.7%) patients had confirmed ER according to the final clinical outcomes. In univariate logistic regression analysis, cirrhosis and hepatitis B infection (P=0.015 and 0.083, respectively), hepatobiliary phase hypointensity (P=0.089), Child-Pugh score (P=0.083), the preoperative platelet count (P=0.003), and rad-score (P<0.001) were correlated with ER. However, after multivariate logistic regression analysis, only the preoperative platelet count and rad-score were included as predictors in the final model. The area under ROC curve (AUC) of the radiomics nomogram to predict ER of small HCC was 0.981 (95% CI: 0.957, 1.00), while the AUC verified by bootstrap is 0.980 (95% CI: 0.962, 1.00), indicating the goodness-of-fit of the final model. Conclusions The radiomics nomogram containing the clinical risk factors and rad-score can be used as a quantitative tool to preoperatively predict individual probability of ER of small HCC.
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Affiliation(s)
- Liting Wen
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Shuping Weng
- Department of Radiology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Chuan Yan
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Rongping Ye
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yuemin Zhu
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lili Zhou
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lanmei Gao
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yueming Li
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Key Laboratory of Radiation Biology, Fujian Medical University, Fujian Province University, Fuzhou, China
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48
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Hu S, Liu J, Feng S, Wang Y, Liu H. LncRNA SUMO1P3 acts as a prognostic biomarker and promotes hepatocellular carcinoma growth and metastasis. Aging (Albany NY) 2021; 13:12479-12492. [PMID: 33902004 PMCID: PMC8148505 DOI: 10.18632/aging.202921] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 01/04/2021] [Indexed: 04/10/2023]
Abstract
Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers, including hepatocellular carcinoma (HCC). However, the biological functions of lncRNA small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) and the underlying mechanisms remain unclear. In this study, we revealed that SUMO1P3 expression was enhanced in HCC tissues and cell lines, positively associating with tumor size and number, poor differentiation, lymphatic and distant metastasis, TNM stage, and poor prognosis in HCC patients. In vitro assays showed that SUMO1P3 depletion reduced HCC cell viability and proliferation by hindering cyclin D1 expression and Akt phosphorylation. SUMO1P3 knockdown induced HCC cell apoptosis, as indicated by increased Bax and cleaved caspase-3 expression and the decreased Bcl-2 level. SUMO1P3 silencing suppressed HCC cell migration and invasion by increasing epithelial marker E-cadherin expression and decreasing mesenchymal marker vimentin expression, as well as reducing matrix metalloproteinase (MMP)-2 and MMP-9 levels. Consistently, SUMO1P3 depletion in HCC cells retarded tumor growth and lung metastasis in vivo. Overall, these results supported the applicability of SUMO1P3 as a useful predictor of HCC prognosis and a potential therapeutic target for HCC patients.
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Affiliation(s)
- Shu Hu
- Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China
| | - Jiancheng Liu
- Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China
| | - Shuying Feng
- Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China
| | - Yue Wang
- Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China
| | - Hongchao Liu
- Medical College, Henan University of Science and Technology, Luoyang 471003, Henan, China
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49
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Flores YN, Datta GD, Yang L, Corona E, Devineni D, Glenn BA, Bastani R, May FP. Disparities in Hepatocellular Carcinoma Incidence, Stage, and Survival: A Large Population-Based Study. Cancer Epidemiol Biomarkers Prev 2021; 30:1193-1199. [PMID: 33737301 DOI: 10.1158/1055-9965.epi-20-1088] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/09/2020] [Accepted: 03/11/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Liver cancer is one of the most rapidly increasing cancers in the United States, and hepatocellular carcinoma (HCC) is its most common form. Disease burden and risk factors differ by sex and race/ethnicity, but a comprehensive analysis of disparities by socioeconomic status (SES) is lacking. We examined the relative impact of race/ethnicity, sex, and SES on HCC incidence, stage, and survival. METHODS We used Surveillance, Epidemiology, and End Results (SEER) 18 data to identify histologically confirmed cases of HCC diagnosed between January 1, 2000 and December 31, 2015. We calculated age-adjusted HCC incidence, stage at diagnosis (local, regional, distant, unstaged), and 5-year survival, by race/ethnicity, SES and sex, using SEER*Stat version 8.3.5. RESULTS We identified 45,789 cases of HCC. Incidence was highest among low-SES Asian/Pacific Islanders (API; 12.1) and lowest in high-SES Whites (3.2). Incidence was significantly higher among those with low-SES compared with high-SES for each racial/ethnic group (P < 0.001), except American Indian/Alaska Natives (AI/AN). High-SES API had the highest percentage of HCC diagnosed at the local stage. Of all race/ethnicities, Blacks had the highest proportion of distant stage disease in the low- and high-SES groups. Survival was greater in all high-SES racial/ethnic groups compared with low-SES (P < 0.001), except among AI/ANs. Black, low-SES males had the lowest 5-year survival. CONCLUSIONS With few exceptions, HCC incidence, distant stage at diagnosis, and poor survival were highest among the low-SES groups for all race/ethnicities in this national sample. IMPACT HCC prevention and control efforts should target low SES populations, in addition to specific racial/ethnic groups.
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Affiliation(s)
- Yvonne N Flores
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), California. .,Center for Cancer Prevention and Control Research and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.,Unidad de Investigación Epidemiológica y en Servicios de Salud, Delegación Morelos, Instituto Mexicano del Seguro Social, Blvd. Benito Juárez No. 31, Colonia Centro, Cuernavaca, México
| | - Geetanjali D Datta
- Center for Cancer Prevention and Control Research and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.,Université de Montréal School of Public Health, Montreal, Canada.,Centre Hospitalier de l'Université de Montréal Research Centre, Montreal, Canada
| | - Liu Yang
- Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Edgar Corona
- Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Divya Devineni
- Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Beth A Glenn
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), California.,Center for Cancer Prevention and Control Research and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Roshan Bastani
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), California.,Center for Cancer Prevention and Control Research and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Folasade P May
- Center for Cancer Prevention and Control Research and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.,Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California.,Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California
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50
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Zhu W, Li J, Zhang Y, Zhu Z, Liu H, Lin Y, Hu A, Zhou J, Ren H, Shi X. Inhibition of HMGB1 Suppresses Hepatocellular Carcinoma Progression via HIPK2-Mediated Autophagic Degradation of ZEB1. Front Oncol 2021; 11:599124. [PMID: 33747917 PMCID: PMC7969871 DOI: 10.3389/fonc.2021.599124] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 01/11/2021] [Indexed: 12/29/2022] Open
Abstract
Autophagy is a conserved catabolic process maintaining cellular homeostasis and reportedly plays a critical role in tumor progression. Accumulating data show that autophagic activity is inhibited in hepatocellular carcinoma. However, the underlying molecular basis of impaired autophagy in HCC remains unclear. In this study, we revealed that autophagic activity was suppressed by HMGB1 in a HIPK2-dependent way. Targeting HMGB1 could inhibit the degradation of HIPK2, as a result of which, autophagic degradation of ZEB1 was enhanced by reprogramming glucose metabolism/AMPK/mTOR axis. Moreover, we demonstrated that selectively degradation of ZEB1 was responsible for HCC growth inhibition in HMGB1 deficient cells. Lastly, we found the combination therapy of HMGB1 inhibitor and rapamycin achieved a better anti-HCC effect. These results demonstrate that impaired autophagy is controlled by HMGB1 and targeting HMGB1 could suppress HCC progression via HIPK2-mediated autophagic degradation of ZEB1.
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Affiliation(s)
- Wei Zhu
- Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yuheng Zhang
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhengyi Zhu
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Hanyi Liu
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yunzhen Lin
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Anyin Hu
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jingchao Zhou
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Haozhen Ren
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaolei Shi
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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