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An Y, Liu W, Deng Y, Huang W, Huang J. SLC7A11-HSPB1 Axis: A Novel Mechanism for Hepatocellular Carcinoma Progression and Ferroptosis Regulation. Biomed J 2025:100869. [PMID: 40339903 DOI: 10.1016/j.bj.2025.100869] [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: 11/19/2024] [Revised: 03/27/2025] [Accepted: 05/02/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND SLC7A11, a plasma membrane protein, has been implicated as an oncogene in various cancers, including hepatocellular carcinoma (HCC). Its role in HCC pathogenesis, particularly in relation to ferroptosis, is not well understood. This study aims to investigate the function of SLC7A11 with ferroptosis and its interaction in development of HCC. METHODS AND MATERIAL Clinical HCC tissue samples were used to analyze the expression of SLC7A11 by RT-PCR. The impact of SLC7A11 on HCC cell viability, proliferation, and migration was assessed by CCK-8, AlamarBlue and Transwell. Protein-protein interactions were explored using co-immunoprecipitation and immunofluorescence. The effect of SLC7A11 on ferroptosis was evaluated by iron levels, ROS, and GSH. The impact of sorafenib and doxorubicin (DOX) on HCC cells was analyzed using cell viability assay. RESULTS SLC7A11 was found to be highly expressed in HCC tissues and was correlated with tumor size and poor prognosis. Overexpression of SLC7A11 in HCC cells promoted cell viability, proliferation, and migration. Additionally, SLC7A11 overexpression mitigated erastin-induced ferroptosis, as evidenced by decreased ROS levels and increased GSH levels. We also discovered that SLC7A11 interacted with HSPB1. HSPB1 inhibited erastin-induced ferroptosis. Furthermore, a portion of the cell death induced by sorafenib and DOX is attributed to ferroptosis, with HSPB1 and SLC7A11 inhibiting the death induced by the two drugs, respectively. CONCLUSIONS SLC7A11 plays a significant role in HCC progression by inhibiting ferroptosis, and its interaction with HSPB1 is a critical pathway in this process. Targeting the SLC7A11-HSPB1 axis may provide a novel therapeutic strategy for HCC treatment, highlighting the importance of understanding the mechanisms of ferroptosis in cancer cells.
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Affiliation(s)
- Yan An
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China; Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China
| | - Weilong Liu
- Institute of Hepatology, National clinical research center for infectious diseases, Guangdong Key Lab for Diagnosis &Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, 518112, China
| | - Yuliang Deng
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Wanqiu Huang
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
| | - Jian Huang
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
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Wang H, Zhu X, Qiu M, Xuan J, Shi X, Huang L, Wang K, Li J. Impact of clinical lymph node status on survival in patients with intrahepatic cholangiocarcinoma undergoing liver resection plus lymphadenectomy. ANZ J Surg 2024; 94:2189-2194. [PMID: 38817200 DOI: 10.1111/ans.19105] [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: 04/13/2024] [Revised: 05/13/2024] [Accepted: 05/14/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUNDS Liver resection plus lymphadenectomy is essential to ensure precise staging in patients with intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the influence of the clinical status of lymph nodes on the survival outcomes in ICC patients. METHODS Between January 2015 and December 2020, consecutive patients diagnosed with ICC who underwent liver resection plus lymphadenectomy were enrolled. Clinical assessment of lymph node status included positron emission tomography/computed tomography examination by radiologists pre-operatively, alongside intraoperative abdominal examination by the surgical team. Retrospective collection and analysis of clinical information alongside survival data were performed to assess outcomes. RESULTS The study included a total of 359 patients, with 291 (81.0%) and 151 (42.1%) displaying clinically and pathologically positive lymph nodes, respectively. The clinical assessment method had a sensitivity of 81.2% and a specificity of 54.3%. Following a median follow-up period of 32 months, the overall survival (OS) rates at 1, 3, and 5 years were 69.1%, 50.6%, and 41.2%, respectively, while the disease-free survival (DFS) rates were 60.7%, 42.8%, and 40.1%, respectively, across the cohort. Patients who had clinically positive but pathologically negative lymph nodes recorded the highest median OS (52 months) and median DFS (32 months). Conversely, those who were clinically negative but pathologically positive experienced the lowest median OS (16 months) and median DFS (8 months). CONCLUSION The current approach to clinically assessing lymph node status in ICC has a significant rate of false positives. Patients with clinically positive but pathologically negative lymph nodes exhibit the most favourable survival outcomes.
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Affiliation(s)
- Hongling Wang
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Xingwu Zhu
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Maixuan Qiu
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Jianbing Xuan
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Xiaodong Shi
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Liang Huang
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Kui Wang
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Jing Li
- Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
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Tu J, Wang B, Wang X, Huo K, Hu W, Zhang R, Li J, Zhu S, Liang Q, Han S. Current status and new directions for hepatocellular carcinoma diagnosis. LIVER RESEARCH 2024; 8:218-236. [PMID: 39958920 PMCID: PMC11771281 DOI: 10.1016/j.livres.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/17/2024] [Accepted: 12/01/2024] [Indexed: 02/18/2025]
Abstract
Liver cancer ranks as the sixth most common cancer globally, with hepatocellular carcinoma (HCC) accounting for approximately 75%-85% of cases. Most patients present with moderately advanced disease, while those with advanced HCC face limited and ineffective treatment options. Despite diagnostic efforts, no ideal tumor marker exists to date, highlighting the urgent clinical need for improved early detection of HCC. A key research objective is the development of assays that target specific pathways involved in HCC progression. This review explores the pathological origin and development of HCC, providing insights into the mechanistic rationale, clinical statistics, and the advantages and limitations of commonly used diagnostic tumor markers. Additionally, it discusses the potential of emerging biomarkers for early diagnosis and offers a brief overview of relevant assay methodologies. This review aims to summarize existing markers and investigate new ones, providing a basis for subsequent research.
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Affiliation(s)
- Jinqi Tu
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China
| | - Bo Wang
- Animal Experimental Center, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Xiaoming Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China
| | - Kugeng Huo
- Cyagen Biosciences (Guangzhou) Inc., Guangzhou, Guangdong, China
| | - Wanting Hu
- MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Key Lab of Microanalytical Methods & Instrumentation, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing, China
| | - Rongli Zhang
- Department of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jinyao Li
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
| | - Shijie Zhu
- Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qionglin Liang
- MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Key Lab of Microanalytical Methods & Instrumentation, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing, China
| | - Shuxin Han
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
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Blažević T, Aničić MN, Ćavar S, Vuković J. Autoimmune Pancreatitis Type 2, Biliary Cysts and Giardia lamblia. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1075. [PMID: 39334608 PMCID: PMC11430033 DOI: 10.3390/children11091075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/03/2024] [Accepted: 08/30/2024] [Indexed: 09/30/2024]
Abstract
Autoimmune pancreatitis type 2 is a relatively novel entity with some still controversial issues. The current diagnostic algorithm relies on imaging studies and histology. Therapy includes corticosteroids with consequently low risk of relapse in the following year. However, the pathogenesis remains unclear, and data are insufficient for long-term prognosis. We have treated a 17-year-old boy whose autoimmune pancreatitis type 2 was revealed during surgery for a pre-existing biliary tract anomaly with concurrent protozoal infection. We discuss the co-occurrence of these conditions in terms of eventual pathogenesis correlation and combined effect on long-term prognosis.
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Affiliation(s)
- Tonka Blažević
- Department of Pediatrics, General Hospital Zadar, BožePeričića5, 23000 Zadar, Croatia
- Department of Pediatrics, School of Medicine, University Hospital Centre Zagreb, University of Zagreb, Kišpatićeva12, 10000 Zagreb, Croatia
| | - Mirna Natalija Aničić
- Department of Pediatrics, School of Medicine, University Hospital Centre Zagreb, University of Zagreb, Kišpatićeva12, 10000 Zagreb, Croatia
| | - Stanko Ćavar
- Department of Surgery, School of Medicine, University Hospital Centre Zagreb, University of Zagreb, Kišpatićeva12, 10000 Zagreb, Croatia
| | - Jurica Vuković
- Department of Pediatrics, School of Medicine, University Hospital Centre Zagreb, University of Zagreb, Kišpatićeva12, 10000 Zagreb, Croatia
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Huang S, Yin Y, Li J, Shi M, Bian H, Zhao L. Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers. Curr Med Chem 2024; 31:6586-6595. [PMID: 37608661 DOI: 10.2174/0929867331666230822121246] [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: 12/07/2022] [Revised: 05/19/2023] [Accepted: 06/15/2023] [Indexed: 08/24/2023]
Abstract
PURPOSE It is critical to assess primary liver cancer patients likely to benefit from radiotherapy (RT) or RT plus chemo-immunotherapy. Many potential peripheral biomarkers from blood samples have been proposed for clinical application. Therefore, the aim of this study was to evaluate treatments with radiotherapy alone and radiotherapy plus chemo-immunotherapy in patients with unresectable primary liver cancer based on blood biomarkers. METHODS From January, 2017, to February, 2022, 63 unresectable primary liver cancer patients receiving radiotherapy alone (RT, n = 21) or radiotherapy plus chemo-immunotherapy (RT plus C/IT, n = 42) were included in this study. We compared the clinical outcomes and adverse effects of these two groups. Also, distant metastasis-free survival (DMFS), overall survival (OS), and progress- free survival (PFS) were retrospectively analyzed. Finally, univariable and multivariable Cox analyses were used to explore the prognostic role of blood biochemical biomarkers. RESULTS In this study, 1, 2, and 3 years of OS after RT treatment were 63.9%, 27.0%, and 13.5%, and after RT plus C/IT were 68.2%, 37.0%, and 24.7%, respectively (p = 0.617). Compared with baseline, white blood cells (WBC) and lymphocytes were significantly decreased after RT (p = 0.002 and p = 0.001, respectively) or RT plus C/IT therapy (p = 0.135 and p<0.001, respectively). In multivariable Cox regression analyses, higher lymphocyte counts before RT (pre-Lymphocyte) were associated with better OS and PFS (HR=0.439, p = 0.023; HR=0.539, p = 0.053; respectively), and higher lymphocyte counts before RT (pre- Platelets) were a poor prognostic factor associated with DMFS (HR=1.013, p = 0.040). Importantly, OS and PFS were significantly better for patients (pre-Lymphocyte ≥1.10 x 109/L) (p = 0.006; p = 0.066, respectively). The DMFS was significantly better for patients (pre-platelets < 233.5 ×109/L) (p<0.001). CONCLUSION Our evaluation of blood biomarkers before and after radiotherapy or plus chem-immunotherapy for primary liver cancer revealed a potential marker for clinics to decide on precise treatment strategies.
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Affiliation(s)
- Shigao Huang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
- Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China
| | - Yutian Yin
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jianping Li
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Mei Shi
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Huijie Bian
- Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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Li S, Dong R, Kang Z, Li H, Wu X, Li T. Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms? Cytokine Growth Factor Rev 2023; 73:93-100. [PMID: 37541791 DOI: 10.1016/j.cytogfr.2023.06.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 06/25/2023] [Accepted: 06/29/2023] [Indexed: 08/06/2023]
Abstract
Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms.
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Affiliation(s)
- Shaodong Li
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China; Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130021, China
| | - Ruizhi Dong
- Department of Colorectal & Anal Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130021, China
| | - Zhenhua Kang
- Department of Colorectal & Anal Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130021, China
| | - Hucheng Li
- Department of Hepato-Pancreato-Biliary Center, Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.
| | - Xueliang Wu
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China; Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China.
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China.
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Gao K, Li X, Ni J, Wu B, Guo J, Zhang R, Wu G. Non-coding RNAs in enzalutamide resistance of castration-resistant prostate cancer. Cancer Lett 2023; 566:216247. [PMID: 37263338 DOI: 10.1016/j.canlet.2023.216247] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 05/23/2023] [Accepted: 05/24/2023] [Indexed: 06/03/2023]
Abstract
Enzalutamide (Enz) is a next-generation androgen receptor (AR) antagonist used to treat castration-resistant prostate cancer (CRPC). Unfortunately, the relapsing nature of CRPC results in the development of Enz resistance in many patients. Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins, which include microRNAs (miRNA), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs with known and unknown functions. Recently, dysregulation of ncRNAs in CRPC, particularly their regulatory function in drug resistance, has attracted more and more attention. Herein, we introduce the roles of dysregulation of different ncRNAs subclasses in the development of CRPC progression and Enz resistance. Recently determined mechanisms of Enz resistance are discussed, focusing mainly on the role of AR-splice variant-7 (AR-V7), mutations, circRNAs and lncRNAs that act as miRNA sponges. Also, the contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are discussed. We summarize the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and highlight the prospect of future therapeutic strategies against Enz resistance.
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MESH Headings
- Male
- Humans
- Prostatic Neoplasms, Castration-Resistant/drug therapy
- Prostatic Neoplasms, Castration-Resistant/genetics
- Prostatic Neoplasms, Castration-Resistant/metabolism
- Receptors, Androgen/genetics
- Receptors, Androgen/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/therapeutic use
- RNA, Circular/genetics
- Drug Resistance, Neoplasm/genetics
- Neoplasm Recurrence, Local
- Nitriles
- Androgen Receptor Antagonists/therapeutic use
- MicroRNAs/genetics
- MicroRNAs/therapeutic use
- Cell Line, Tumor
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Affiliation(s)
- Ke Gao
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China; The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
| | - Xiaoshun Li
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China.
| | - Jianxin Ni
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China.
| | - Bin Wu
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China.
| | - Jiaheng Guo
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China; The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
| | - Rui Zhang
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China; The State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, China.
| | - Guojun Wu
- Department of Urology, Xi'an People's Hospital(Xi'an Fourth Hospital), School of Life Sciences and Medicine, Northwest University, Xi'an, 710199, China.
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Liu M, Zhang Z, Zhang W, Liu SM. Advances in biomarker discovery using circulating cell-free DNA for early detection of hepatocellular carcinoma. WIREs Mech Dis 2023; 15:e1598. [PMID: 36697374 PMCID: PMC10176863 DOI: 10.1002/wsbm.1598] [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: 08/18/2022] [Revised: 10/21/2022] [Accepted: 01/12/2023] [Indexed: 01/27/2023]
Abstract
The past several decades have witnessed unprecedented progress in basic and clinical cancer research, and our understanding of the molecular mechanisms and pathogenesis of cancers have been greatly improved. More recently, with the availability of high-throughput sequencing and profiling platforms as well as sophisticated analytical tools and high-performance computing capacity, there have been tremendous advances in the development of diagnostic approaches in clinical oncology, especially the discovery of novel biomarkers for cancer early detection. Although tissue biopsy-based pathology has been the "gold standard" for cancer diagnosis, notable limitations such as the risk due to invasiveness and the bias due to intra-tumoral heterogeneity have limited its broader applications in oncology (e.g., screening, regular disease monitoring). Liquid biopsy analysis that exploits the genetic and epigenetic information contained in DNA/RNA materials from body fluids, particularly circulating cell-free DNA (cfDNA) in the blood, has been an intriguing alternative approach because of advantageous features such as sampling convenience and minimal invasiveness. Taking advantage of innovative enabling technologies, cfDNA has been demonstrated for its clinical potential in cancer early detection, including hepatocellular carcinoma (HCC), the most common liver cancer that causes serious healthcare burden globally. Hereby, we reviewed the current advances in cfDNA-based approaches for cancer biomarker discovery, with a focus on recent findings of cfDNA-based early detection of HCC. Future clinical investigations and trials are warranted to further validate these approaches for early detection of HCC, which will contribute to more effective prevention, control, and intervention strategies with the ultimate goal of reducing HCC-associated mortality. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics.
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Affiliation(s)
- Mingjun Liu
- Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
- Department of Clinical Laboratory, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Zhou Zhang
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Wei Zhang
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Institute of Precision Medicine, Jining Medical University, Jining, Shandong Province, China
| | - Song-Mei Liu
- Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
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Hussein MA, Radwan AFM, Fawzi MM, Rashed LA, Saad EHAI. MicroRNA 21as a novel biomarker in hepatitis C virus-related hepatocellular carcinoma. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00136-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is considered one of the most common cancers occurring in human population all over the world. It became an increasingly threatening malignancy due to both morbidity and mortality. Chronic viral hepatitis B and hepatitis C are two risk factors, which account for 80–90% of all HCC cases worldwide. Alfa Feto protien is used as a tumor marker for HCC diagnosis and prognosis prediction; however, its false negative rate when used alone is as high as 40% for patients with early-stage HCC. AFP levels remain normal in 15–30% of all the patients, even patients with advanced HCC. It has been demonstrated that miRNAs (MicroRNAs) are an important class of non-coding RNAs. They act as tumor oncogenes or suppressors and are involved in the HCC development. MiRNAs are endogenous nucleotides that can be found in intra- and extracellular spaces, such as the blood, urine, and saliva.
The study evaluated the miRNA 21 as a novel biomarker in patients with HCV related hepatocellular carcinoma.
Results
The study was conducted on three groups. Group (1) included 25 patients with liver cirrhosis due to hepatitis C virus infection. Group (2) included 25 patients with hepatocellular carcinoma (HCC) on top of liver cirrhosis due to hepatitis C virus infection. Group (3) included 10 normal control subjects. There was a significant difference in the mean level of miRNA between the three groups with p value < 0.001 with the highest value in group 2 ( 8.28 ± 2.55), then in group1 (5.04 ± 2.11) and the lowest in group 3 (control) (1.02 ± 0.07). MiRNA 21 has a sensitivity of 68% and a specificity of 96%, to differentiate between the liver cirrhosis group and HCC group.
Conclusion
miRNA 21 can be a promising marker for detection of patients with HCV-related hepatocellular carcinoma, with higher specificity compared to α feto protein; however, its cost is higher.
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Chen C, Su J, Wu H, Qiu Y, Song T, Mao X, He Y, Cheng Z, Zhai W, Li J, Geng Z, Tang Z. Prognostic value of lymphadenectomy in node-negative intrahepatic cholangiocarcinoma: A multicenter, retrospectively study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 49:780-787. [PMID: 36404249 DOI: 10.1016/j.ejso.2022.11.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 09/24/2022] [Accepted: 11/03/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND This study aimed to evaluate the prognostic value of lymph node dissection (LND) in node-negative intrahepatic cholangiocarcinoma (ICC) and identify the appropriately total number of lymph nodes examined (TNLE). METHODS Data from node-negative ICC patients who underwent curative intent resection in ten Chinese hepatobiliary centers from January 2010 to December 2018 were collected. Overall survival (OS), relapse-free survival (RFS) and postoperative complications were analyzed. Propensity score matching (PSM) was performed to reduce the bias due to confounding variables in LND group and non-lymph node dissection (NLND) group. The optimal TNLE was determined by survival analysis performed by the X-tile program using the enumeration method. RESULTS A total of 637 clinically node-negative ICC patients were included in this study, 74 cases were found lymph node (LN) positive after operation. Among the remaining 563 node-negative ICC patients, LND was associated with longer OS but not RFS before PSM (OS: 35.4 vs 26.0 months, p = 0.047; RFS: 15.0 vs 15.4 months, p = 0.992). After PSM, patients in LND group had better prognosis on both OS and RFS (OS: 38.0 vs 23.0 months, p < 0.001; RFS: 15.0 vs 13.0 months, p = 0.029). There were no statistically differences in postoperative complications. When TNLE was greater than 8, OS (48.5 vs 31.1 months, p = 0.025) and RFS (21.0 vs 13.0 months, p = 0.043) were longer in the group with more dissected LNs. CONCLUSION Routinely LND for node-negative ICC patients is recommended for it helps accurate tumor staging and associates with better prognosis. The optimal TNLE is more than 8.
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Ji H, Barr Fritcher EG, Yin J, Bainter TM, Zemla TJ, Gores GJ, Halling KC, Kipp BR, Roberts LR. Evaluating the Significance of Pancreatobiliary Fluorescence In Situ Hybridization Polysomy on Prognosis in De Novo Cholangiocarcinoma. Clin Transl Gastroenterol 2022; 13:e00523. [PMID: 36000989 PMCID: PMC9624591 DOI: 10.14309/ctg.0000000000000523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 06/30/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION We recently developed a fluorescence in situ hybridization probe set for evaluating suspicious biliary and pancreatic duct strictures (PB-FISH). We aimed to determine whether PB-FISH results in biliary brush cytology specimens are associated with outcomes of patients with cholangiocarcinoma (CCA). METHODS We performed a retrospective study of patients with CCA tested by PB-FISH from January 2015 to August 2018. CCA was stratified by primary sclerosing cholangitis (PSC) into those with (PSC CCA) or without PSC ( de novo CCA). PB-FISH results were categorized as polysomy (gain of multiple loci), nonpolysomy (single locus gain, single locus gain with 9p21 loss, homozygous 9p21 loss, tetrasomy), and disomy (no abnormalities). Overall survival (OS) was estimated using Kaplan-Meier methods and compared between the PB-FISH results using log-rank tests. Cox models were adjusted for age, sex, CA 19-9, cytology results, source of brushing sample, and treatments. RESULTS Characteristics of 264 eligible patients (median age 60.4; range 18-92) were comparable for patients with PB-FISH polysomy vs nonpolysomy vs disomy. The median OS was similar between disomy, nonpolysomy, and polysomy in the overall population (22.7 vs 22.7 vs 20.3 months, respectively). For de novo CCA, both polysomy and nonpolysomy were associated with worse OS compared with disomy (polysomy: hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.14-3.83; nonpolysomy: HR = 2.4, 95% CI = 0.54-2.46; P = 0.027). For PSC CCA, neither polysomy nor nonpolysomy were significantly associated with worse OS (polysomy: 0.90, 95% CI = 0.47-1.75; nonpolysomy: HR = 1.78, CI = 0.71-4.49; P = 0.27). DISCUSSION PB-FISH alterations are associated with worse survival in de novo CCA, though statistical significance was lost when adjusting for confounding variables.
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Affiliation(s)
- Hyun Ji
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Jun Yin
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Tiffany M. Bainter
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Tyler J. Zemla
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kevin C. Halling
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Benjamin R. Kipp
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Ji J, Yang W, Shi HB, Liu S, Zhou WZ. Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study. BMC Gastroenterol 2022; 22:321. [PMID: 35768773 PMCID: PMC9241260 DOI: 10.1186/s12876-022-02387-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 06/13/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose To compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE–MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection. Materials and methods From June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE–MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated. Results The TACE–MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE–MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE–MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE–MWA group had a significantly lower number of re-TACE sessions (P = 0.003). Conclusions Although TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE–MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.
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Affiliation(s)
- Jie Ji
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei-Zhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.
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Zhou D, Wang Y, Hu H, Liu H, Deng J, Li L, Zheng C. lncRNA MALAT1 promotes HCC metastasis through the peripheral vascular infiltration via miRNA-613: a primary study using contrast ultrasound. World J Surg Oncol 2022; 20:203. [PMID: 35706002 PMCID: PMC9202184 DOI: 10.1186/s12957-022-02655-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 05/26/2022] [Indexed: 11/24/2022] Open
Abstract
Background This study aimed to explore the specific pathogenesis of lncRNA MALAT1 promoting the invasion and metastasis of hepatocellular carcinoma (HCC) through peripheral blood vessels by regulating the expression of miRNA-613 molecule. Methods The data of 60 HCC metastatic patients and 60 HCC non-metastatic patients detected by the contrast-enhanced ultrasound (CEUS) in the Second Affiliated Hospital of Qiqihar Medical College from January 2020 to June 2021 were collected, as well as postoperatively retained HCC tissues and paired paracancer tissues (5 cm laterally from the edge of the cancer area), to study the changes of microangiogenesis in HCC tissues with CEUS. The correlation between CEUS grading and lncRNA MALAT1 in patients with HCC was analyzed through Pearson correlation analysis, lncRNA MALAT1 and miRNA-613 in HCC tissues of patients with HCC were detected by qRT-PCR, followed by the bioinformatic analysis for the relationship between lncRNA MALAT1 and miRNA-613. The Log-growing human HCC cell strain, HepG2, was selected for experiments. Adenovirus transfection knocked down lncRNA MALAT1 in HCC cells, which was divided into two groups (inhibitor-NC group and lncR-inhibitor group), followed by knocking down miRNA-613 on the basis of knocking down lncRNA MALAT1, which was divided into three groups (inhibitor-NC group, lncR-inhibitor groups, and lncR/miR613-inhibitor group). The expression of miRNA-613 and lncRNA MALAT1 in each group was detected by qRT-PCR. The migration and invasiveness of cells in each group were detected by Transwell assay. Results CEUS of HCC and Pearson correlation analysis showed that CEUS grading and lncRNA MALAT1 were positively correlated in patients with HCC. In HCC tissues of patients with HCC, lncRNA MALAT1 expressed high and miRNA-613 expressed low. The results of bioinformatic analysis showed the targeting of lncRNA MALAT1 and miRNA-613. Knocking down lncRNA MALAT1 could increase miRNA-613 expression significantly, and reduce the migration of HCC cells. Inhibiting miRNA-613 based on knocking down lncRNA MALAT1 could increase the survival and migration of HCC cells. Conclusions lncRNA MALAT1 can promote HCC metastasis through the peripheral vascular infiltration by inhibiting the level of MiRNA-613, which can, therefore, be used as a potential target for the treatment of HCC. 1. Contrast-enhanced ultrasound (CEUS) grading was positively correlated with lncRNA MALAT1 in patients with hepatocellular carcinoma (HCC). 2. lncRNA MALAT1 expressed high and miRNA-613 expressed low in HCC tissues of patients with HCC. 3. lncRNA MALAT1 was targeted with miRNA-613. 4. Knocking down lncRNA MALAT1 could significantly increase miRNA-613 expression. 5. Knocking down lncRNA MALAT1 could reduce the migration of HCC cells. 6. Inhibiting miRNA-613 on the basis of knocking down lncRNA MALAT1 could increase the survival and migration of HCC cells.
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Affiliation(s)
- Dandan Zhou
- Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
| | - Ying Wang
- Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China.
| | - Haifeng Hu
- Department of Magnetic Resonance Imaging, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
| | - Huilin Liu
- Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
| | - Jiajia Deng
- Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
| | - Lu Li
- Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
| | - Chunlei Zheng
- Department of Oncology, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China
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Chromosomal aberrations, visualized using UroVysion® fluorescence in-situ hybridization assay, can predict poor prognosis in formalin-fixed paraffin-embedded tissues of cholangiocarcinoma patients. Hum Pathol 2022; 126:31-44. [DOI: 10.1016/j.humpath.2022.05.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/29/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022]
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Wang P, Nie F, Dong T, Yang D, Liu T, Wang G. Diagnostic Value of CEUS LI-RADS Version 2017 in Differentiating AFP-Negative Hepatocellular Carcinoma from Other Primary Malignancies of the Liver. Diagnostics (Basel) 2021; 11:diagnostics11122250. [PMID: 34943487 PMCID: PMC8699975 DOI: 10.3390/diagnostics11122250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 11/16/2022] Open
Abstract
Purpose: To explore the diagnostic value of Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) in differentiating alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) from other primary malignancies (OM) of the liver. Methods: The data of 99 patients with primary liver malignant tumors confirmed by surgical pathology and AFP-negative from January 2018 to January 2021 were retrospectively analyzed, and the lesions were divided into 61 cases in the AFP-negative HCC group and 38 cases in the OM group according to the pathological findings, the CEUS features of the lesions were analyzed and the lesions were classified according to the CEUS LI-RADS v2017. Comparison of CEUS features between the two groups was performed using the χ2 test. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of CEUS LI-RADS v2017 for the diagnosis of AFP-negative HCC and OM were calculated using pathological findings as the gold standard. Results: The differences in features of arterial phase enhancement and wash-out between the HCC and OM groups were statistically significant (p < 0.05). The sensitivity of diagnosing HCC by LR-5 was 62.3% and the specificity was 92.1%. The sensitivity of diagnosing OM by LR-M was 92.1% and the specificity was 83.6%. Conclusions: When AFP is negative in patients with intrahepatic focal lesions, LR-5 has high specificity but low sensitivity in the diagnosis of HCC, and LR-M has high sensitivity and specificity in the diagnosis of OM. CEUS LI-RADS is a tool to differentiate AFP-negative HCC and OM effectively.
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Affiliation(s)
| | - Fang Nie
- Correspondence: ; Tel.: +86-13993163088
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Feng J, Zhu R, Yin Y, Wang S, Zhou L, Lv F, Zhao D. Re-Recognizing the Cellular Origin of the Primary Epithelial Tumors of the Liver. J Hepatocell Carcinoma 2021; 8:1537-1563. [PMID: 34917552 PMCID: PMC8668194 DOI: 10.2147/jhc.s334935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/25/2021] [Indexed: 11/29/2022] Open
Abstract
The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cells-of-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.
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Affiliation(s)
- Jiliang Feng
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
- Correspondence: Jiliang Feng Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai Street, FengTai District, Beijing, 100069, People’s Republic of ChinaTel +86-10-83997342Fax +86-10-83997343 Email
| | - Ruidong Zhu
- General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Yu Yin
- Department of Pathology, Anhui Medical University, Hefei, 230032, People’s Republic of China
| | - Shanshan Wang
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Lei Zhou
- Department of Pathology, First Affiliated Hospital of Bengbu Medical College/Bengbu Medical College, Bengbu, 233004, People’s Republic of China
| | - Fudong Lv
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China
| | - Dawei Zhao
- Department of Medical Imaging, Capital Medical University, Beijing, 100069, People’s Republic of China
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Ney A, Garcia-Sampedro A, Goodchild G, Acedo P, Fusai G, Pereira SP. Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum. Front Oncol 2021; 11:699401. [PMID: 34660269 PMCID: PMC8515053 DOI: 10.3389/fonc.2021.699401] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 09/15/2021] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.
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Affiliation(s)
- Alexander Ney
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Andres Garcia-Sampedro
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - George Goodchild
- St. Bartholomew's hospital, Barts Health NHS Trust, London, United Kingdom
| | - Pilar Acedo
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Giuseppe Fusai
- Division of Surgery and Interventional Science - University College London, London, United Kingdom
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
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Yu Z, Zhang Y, Shao S, Liu Q, Li Y, Du X, Zhang K, Zhang M, Yuan H, Yuan Q, Liu T, Gao Y, Wang Y, Hong W, Han T. Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma. Front Oncol 2021; 11:755814. [PMID: 34660326 PMCID: PMC8517522 DOI: 10.3389/fonc.2021.755814] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/09/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear. METHODS The differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments. RESULTS The level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2. CONCLUSIONS CDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.
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Affiliation(s)
- Zhenjun Yu
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Yu Zhang
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Shuai Shao
- Department of Hepatology and Gastroenterology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, China
| | - Qi Liu
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Yuhan Li
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Xiaoxiao Du
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Kun Zhang
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Mengxia Zhang
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Haixia Yuan
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Qiang Yuan
- Department of Hepatobiliary Surgery, The Tianjin Third Central Hospital, Tianjin, China
| | - Tong Liu
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, The Tianjin Third Central Hospital, Tianjin, China
| | - Yingtang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, The Tianjin Third Central Hospital, Tianjin, China
| | - Yijun Wang
- Department of Hepatobiliary Surgery, The Tianjin Third Central Hospital, Tianjin, China
| | - Wei Hong
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Tao Han
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
- Department of Hepatology and Gastroenterology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, The Tianjin Third Central Hospital, Tianjin, China
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Guerrini GP, Berretta M, Guaraldi G, Magistri P, Esposito G, Ballarin R, Serra V, Di Sandro S, Di Benedetto F. Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience. Cancers (Basel) 2021; 13:cancers13184727. [PMID: 34572954 PMCID: PMC8471924 DOI: 10.3390/cancers13184727] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. AIM To address the results of liver transplantation (LT) for HCC in HIV-infected patients. METHODS All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. RESULTS Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. CONCLUSION Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.
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Affiliation(s)
- Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Massimiliano Berretta
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy;
| | - Giovanni Guaraldi
- Infectious Diseases Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy;
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Giuseppe Esposito
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Roberto Ballarin
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Valentina Serra
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy; (G.P.G.); (P.M.); (G.E.); (R.B.); (V.S.); (S.D.S.)
- Correspondence:
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Li K, Yao T, Zhang Y, Li W, Wang Z. NEAT1 as a competing endogenous RNA in tumorigenesis of various cancers: Role, mechanism and therapeutic potential. Int J Biol Sci 2021; 17:3428-3440. [PMID: 34512157 PMCID: PMC8416723 DOI: 10.7150/ijbs.62728] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 07/24/2021] [Indexed: 12/24/2022] Open
Abstract
The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) that is upregulated in a variety of human cancer types. Increasing evidence has shown that the elevation of NEAT1 in cancer cells promotes cell growth, migration, and invasion and inhibits cell apoptosis. It is also known that lncRNAs act as a competing endogenous RNA (ceRNA) by sponging microRNAs (miRNAs) to alter the expression levels of their target genes in the development of cancers. Therefore, it is important to understand the molecular mechanisms underlying this observation. In this review, specific emphasis was placed on NEAT1's role in tumor development. We also summarize and discuss the feedback roles of NEAT1/miRNA/target network in the progression of various cancers. As our understanding of the role of NEAT1 during tumorigenesis improves, its therapeutic potential as a biomarker and/or target for cancer also becomes clearer.
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Affiliation(s)
- Kun Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
| | - Tongyue Yao
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
| | - Yu Zhang
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
| | - Wen Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
| | - Ziqiang Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.,Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China
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21
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Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma. Int J Mol Sci 2021; 22:ijms22126569. [PMID: 34207359 PMCID: PMC8233871 DOI: 10.3390/ijms22126569] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/13/2021] [Accepted: 06/16/2021] [Indexed: 01/11/2023] Open
Abstract
Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.
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Zhang F, Wang Y, Chen G, Li Z, Xing X, Putz-Bankuti C, Stauber RE, Liu X, Madl T. Growing Human Hepatocellular Tumors Undergo a Global Metabolic Reprogramming. Cancers (Basel) 2021; 13:1980. [PMID: 33924061 PMCID: PMC8074141 DOI: 10.3390/cancers13081980] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/14/2021] [Accepted: 04/16/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis, high morbidity and mortality concerning with lack of effective diagnosis and high postoperative recurrence. Similar with other cancers, HCC cancer cells have to alter their metabolism to adapt to the changing requirements imposed by the environment of the growing tumor. In less vascularized regions of tumor, cancer cells experience hypoxia and nutrient starvation. Here, we show that HCC undergoes a global metabolic reprogramming during tumor growth. A combined proteomics and metabolomics analysis of paired peritumoral and tumor tissues from 200 HCC patients revealed liver-specific metabolic reprogramming and metabolic alterations with increasing tumor sizes. Several proteins and metabolites associated with glycolysis, the tricarboxylic acid cycle and pyrimidine synthesis were found to be differentially regulated in serum, tumor and peritumoral tissue with increased tumor sizes. Several prognostic metabolite biomarkers involved in HCC metabolic reprogramming were identified and integrated with clinical and pathological data. We built and validated this combined model to discriminate against patients with different recurrence risks. An integrated and comprehensive metabolomic analysis of HCC is provided by our present work. Metabolomic alterations associated with the advanced stage of the disease and poor clinical outcomes, were revealed. Targeting cancer metabolism may deliver effective therapies for HCC.
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Affiliation(s)
- Fangrong Zhang
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria;
- BioTechMed-Graz, Mozartgasse 12/II, 8010 Graz, Austria
| | - Yingchao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; (Y.W.); (G.C.); (Z.L.); (X.X.)
| | - Geng Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; (Y.W.); (G.C.); (Z.L.); (X.X.)
| | - Zhenli Li
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; (Y.W.); (G.C.); (Z.L.); (X.X.)
| | - Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; (Y.W.); (G.C.); (Z.L.); (X.X.)
| | - Csilla Putz-Bankuti
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (C.P.-B.); (R.E.S.)
| | - Rudolf E. Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (C.P.-B.); (R.E.S.)
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China; (Y.W.); (G.C.); (Z.L.); (X.X.)
- Xiamen Institute of Rare Earth Materials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Xiamen 361024, China
| | - Tobias Madl
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria;
- BioTechMed-Graz, Mozartgasse 12/II, 8010 Graz, Austria
- Xiamen Institute of Rare Earth Materials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Xiamen 361024, China
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Kelgeri C, Renz D, McGuirk S, Schmid I, Sharif K, Baumann U. Liver Tumours in Children: The Hepatologist's View. J Pediatr Gastroenterol Nutr 2021; 72:487-493. [PMID: 33264187 DOI: 10.1097/mpg.0000000000003006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
ABSTRACT Diagnostic and therapeutic innovations have changed the way we now approach liver tumours in children and adolescents. Novel imaging tools, increasing awareness, and surveillance has led to early diagnosis of benign and malignant liver tumours. Multidisciplinary interventions have favourably altered the natural course in some liver tumours. The role of liver transplantation is expanding and has become fully integrated into today's therapeutic algorithms. Transarterial locoregional and ablation therapies have been successful in adults and are being explored in children to facilitate resectability and improve outcome. For the first time, North American, Japanese, and European experts have designed a global trial to optimize management of malignant liver tumours and aim to find signature molecular profiles that will translate to individualised treatment strategies.This article aims to offer an overview of recent advances in our understanding of liver tumours in children. It focuses on the paediatric hepatologist's view and their role in the multidisciplinary management of benign and malignant liver tumours.
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Affiliation(s)
- Chayarani Kelgeri
- Paediatric Liver Unit including Intestinal Transplantation, Birmingham Women's and Children's NHS Foundation Trust, UK
| | - Diane Renz
- Institute of Diagnostic and Interventional Radiology, Department of Paediatric Radiology, Medizinische Hochschule Hannover, Germany
| | - Simon McGuirk
- Department of Radiology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Irene Schmid
- Paediatric Oncology, Ludwig Maximilians University, Munich, Germany
| | - Khalid Sharif
- Paediatric Liver Unit including Intestinal Transplantation, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Ulrich Baumann
- Paediatric Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany
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24
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Nerve growth factor regulates liver cancer cell polarity and motility. Mol Med Rep 2021; 23:288. [PMID: 33649819 PMCID: PMC7905331 DOI: 10.3892/mmr.2021.11927] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023] Open
Abstract
Nerve growth factor (NGF), a prototypical neurotrophic factor essential for neuronal cell proliferation and survival, has been implicated as a marker of tumor progression, as well as a potential target for novel therapeutic approaches in cancer. To investigate the functional potential of NGF in liver cancer in the present study, a stable NGF-overexpressing HepG2 cell line was generated. The scratch-wound assay was used to investigate cell motility and polarity. Western blotting was performed to evaluate the expression levels of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin, N-cadherin and vimentin. Moreover, immunofluorescence was performed to investigate the arrangement of the actin cytoskeleton. Cell anoikis resistance was examined using a suspension culture model and cell apoptosis was examined via flow cytometry. The present results indicated that NGF overexpression in HepG2 cells disrupted HepG2 cell polarity and promoted cell motility. Furthermore, NGF overexpression induced EMT and actin cytoskeleton rearrangement in HepG2 cells, as well as enhanced anoikis resistance and prevented cellular apoptosis. Notably, a tropomyosin receptor kinase A receptor inhibitor blocked NGF-induced cell motility and apoptosis. Therefore, it was suggested that NGF serves a critical role in the invasion and metastasis of liver cancer. The use of NGF as a biomarker or potential new target could lead to the development of novel factors for diagnosis or for improving therapeutic strategies in liver cancer.
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25
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Serum Golgi protein 73 as a sensitive biomarker for early detection of hepatocellular carcinoma among Egyptian patients with hepatitis C virus-related cirrhosis. Med J Armed Forces India 2021; 77:331-336. [PMID: 34305287 DOI: 10.1016/j.mjafi.2020.11.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 11/12/2020] [Indexed: 11/23/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Early detection of HCC is always a challenging task for physicians. Serum Golgi protein 73 (GP73) is considered a potential tumor marker for the detection of HCC. However, the diagnostic value of GP73 for the HCC diagnosis is still controversial. This research was designed to assess the diagnostic efficacy of GP73 as a diagnostic tool for HCC in cases with hepatitis C virus-related cirrhosis. Methods Eighty-seven subjects were allocated into four different groups in this prospective research (HCC, liver cirrhosis, chronic hepatitis C, and healthy control group). Serum alpha-fetoprotein (AFP) and GP73 were tested for all subjects in the study. Detection of focal hepatic lesions was based on imaging by abdominal ultrasonography and triphasic computed tomography. Results The cut-off values for GP73 and AFP were 534.5 ng/L and 32 ng/mL, respectively. The specificity of GP73 was 87%, and the sensitivity was 88%, while the specificity and sensitivity of AFP levels were 80% and 72%, respectively. The negative predictive value of GP73 was 87.5%, and the positive predictive value of GP73 was 84.6%, while the same parameters of AFP were 73.1% and 75%, respectively. Conclusion Serum Golgi protein 73 could be a valuable biomarker and a useful diagnostic tool for the early diagnosis of HCC in cases of hepatitis C virus-related cirrhosis.
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26
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Zhang X, Ma L, Zhai L, Chen D, Li Y, Shang Z, Zhang Z, Gao Y, Yang W, Li Y, Pan Y. Construction and validation of a three-microRNA signature as prognostic biomarker in patients with hepatocellular carcinoma. Int J Med Sci 2021; 18:984-999. [PMID: 33456356 PMCID: PMC7807177 DOI: 10.7150/ijms.49126] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 12/19/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC), a common type of primary liver cancer, is one of the most aggressive malignant tumors worldwide. Although overall survival (OS) rates for HCC has significantly improved in recent years, however, the exact predictive value of microRNA (miRNA) for the prognosis of HCC has not yet been recognized. Here, we aimed to identify potential prognostic miRNAs involved in HCC by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. The RNA expression profiles and corresponding clinical information of HCC were available from The Cancer Genome Atlas (TCGA) datasets. Differentially expression and standardization analysis of miRNAs, Kaplan-Meier curve and time dependent ROC curve were performed by using R tools. Differentially expressed miRNAs (DEmiRNAs) and clinical parameters involved in the OS of HCC were confirmed by Cox regression models. And functional enrichment analysis was used to establish functions of the targeted genes of DEmiRNAs. A total of 300 DEmiRNAs were significantly related with HCC, of which 40 were down-regulated and 260 were up-regulated. A total of 344 patients with DEmiRNAs, status, overall survival (OS) time were randomized into training group (172) and test group (172). Multivariate Cox regression analyses revealed that 3 miRNA (hsa-miR-139-3p, hsa-miR-760, hsa-miR-7-5p) had independent prognostic significance for the OS of HCC in both training and test group. Moreover, according to Kaplan Meier analysis, the OS of HCC patients with high-risk score was shorter in validation and entire series. The time dependent ROC curve demonstrated high accuracy of the signature for OS. Besides, target genes of three miRNAs were analyzed by functional enrichment analysis and 20 genes associated with OS were verified by using Kaplan-Meier method. Compared with normal and benign group, the relative expression level of hsa-miR-139-3p was significantly decreased, while hsa-miR-7-5p and hsa-miR-760 were distinctly increased in the plasma of HCC patients. The same results were observed in the independent cohort. Collectively, our research suggested that three-miRNA signature could serve as an independent prognostic indicator for HCC patients.
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Affiliation(s)
- Xi Zhang
- Department of Clinical Laboratory, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Li Ma
- Department of Clinical Laboratory, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Li Zhai
- Department of Clinical Laboratory, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Dong Chen
- Department of Ultrasound, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Yong Li
- Department of Abdominal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Zhongjun Shang
- Department of Hospital Affairs, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Zongmei Zhang
- Department of Pathology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Yanzhang Gao
- Department of Clinical Laboratory, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Wei Yang
- Department of Clinical Laboratory, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Yixun Li
- Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Experimental Diagnosis, Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, P.R. China
| | - Yuqing Pan
- Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Experimental Diagnosis, Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, P.R. China
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27
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Huo Q, Ma Y, Yin Y, Qin G. Biomarker Identification for Liver Hepatocellular Carcinoma and Cholangiocarcinoma Based on Gene Regulatory Network Analysis. Curr Bioinform 2021. [DOI: 10.2174/1574893615666200317115609] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Background:
Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL)
are two main histological subtypes of primary liver cancer with a unified molecular landscape, and
feed-forward loops (FFLs) have been shown to be relevant in these complex diseases.
Objective:
To date, there has been no comparative analysis of the pathogenesis of LIHC and CHOL
based on regulatory relationships. Therefore, we investigated the common and distinct regulatory
properties of LIHC and CHOL in terms of gene regulatory networks.
Method:
Based on identified FFLs and an analysis of pathway enrichment, we constructed pathway-specific co-expression networks and further predicted biomarkers for these cancers by network clustering.
Resul:
We identified 20 and 36 candidate genes for LIHC and CHOL, respectively. The literature
from PubMed supports the reliability of our results.
Conclusion:
Our results indicated that the hsa01522-Endocrine resistance pathway was associated
with both LIHC and CHOL. Additionally, six genes (SPARC, CTHRC1, COL4A1, EDIL3, LAMA4
and OLFML2B) were predicted to be highly associated with both cancers, and COL4A2, CSPG4,
GJC1 and ADAMTS7 were predicted to be potential biomarkers of LIHC, and COL6A3, COL1A2,
FAP and COL8A1 were predicted to be potential biomarkers of CHOL. In addition, we inferred that
the Collagen gene family, which appeared more frequently in our overall prediction results, might be
closely related to cancer development.
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Affiliation(s)
- Qiuyan Huo
- School of Computer Science and Technology, Xidian University, Xi’an,China
| | - Yuying Ma
- School of Computer Science and Technology, Xidian University, Xi’an,China
| | - Yu Yin
- School of Computer Science and Technology, Xidian University, Xi’an,China
| | - Guimin Qin
- School of Computer Science and Technology, Xidian University, Xi’an,China
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28
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Raevskaya O, Appelman H, Razumilava N. A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma. ACTA ACUST UNITED AC 2020; 19:478-485. [PMID: 33415066 DOI: 10.1007/s11901-020-00556-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Purpose of review To provide updates on terminology, epidemiology, diagnosis, and treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Recent findings cHCC-CCAs are tumors that in the same nodule contain a variable degree of HCC and CCA components with a transition zone. cHCC-CCAs develop in cirrhotic and non-cirrhotic livers like and is associated with poor outcomes. Mutations in TP53, TERT promoter, and ARID1A are the most common genetic aberrations in cHCC-CCA. Fusion gene PTMS-AP1G1 is unique for cHCC-CCA. A biopsy is required for diagnosis. Surgical resection remains treatment of choice, while liver transplantation for early cHCC-CCA is associated with favorable outcomes. Gemcitabine-based therapy shows benefits for advanced cHCC-CCA. Summary cHCC-CCAs are a heterogeneous group of primary liver cancers with unique biological behavior. Multicenter studies are required for a molecular analysis to inform novel therapeutic approaches, and understand epidemiology and benefits of liver transplantation, liver-directed and targeted therapies for this rare aggressive cancer.
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Affiliation(s)
- Olga Raevskaya
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Henry Appelman
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
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circCDYL Acts as a Tumor Suppressor in Triple Negative Breast Cancer by Sponging miR-190a-3p and Upregulating TP53INP1. Clin Breast Cancer 2020; 20:422-430. [DOI: 10.1016/j.clbc.2020.04.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/27/2020] [Accepted: 04/12/2020] [Indexed: 12/24/2022]
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30
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Ding Y, Sun Z, Zhang S, Han X, Li Y, Xu Q, Zhou L, Xu H, Bai Y, Xu C, Ding H, Ge Y, Wang W. Down-regulation of small nuclear RNA (snRNA) RNU5E-1 in hepatocellular carcinoma presents with vital clinical significance. J Gastrointest Oncol 2020; 11:738-746. [PMID: 32953157 DOI: 10.21037/jgo-20-49] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background For lack of accurate diagnosis and ideal prognosis assessment, hepatocellular carcinoma (HCC) has become the fourth cancers-related death malignant diseases. Small nuclear RNAs (snRNAs) have been investigated as a new class of regulators associated with pathogenesis and clinical evaluation of tumors such as HCC. As for RNU5E-1, one newly identified snRNA, may have similar functions. However, the relationship between RNU5E-1 expression and HCC tumorigenesis remains unclear. Methods The relative RNU5E-1 expression was measured in several HCC cell lines and HCC tissues of 100 patients using quantitative real-time PCR. All patients were grouped according to individual RNU5E-1 expression. Then, the potential association between RNU5E-1 expression in HCC clinical characteristics and prognostic information of patients was evaluated. Results Compared to human normal hepatocyte cell line QSG-7701, the RNU5E-1 expression in HCC cell lines (fold change: SK-HEP-1, 0.417; Hep 3B, 0.313; Huh-7, 0.189) were significantly down-regulated (P<0.05). Similarly, its expression levels were remarkably lower in HCC tissue than that in corresponding adjacent liver tissues (average fold change: 0.322, P=0.002). Besides, the expression level of RNU5E-1 was remarkably related to tumor size, vessel carcinoma embolus, differentiation level, TNM stages and tumor recurrence rate as well as long-term survival in HCC patients (P<0.05). Moreover, in Kaplan-Meier and Cox regression analysis, RNU5E-1 expression was remarkably correlated to postoperative tumor-free as well as long-term survival in HCC patients as independent factors (P<0.05). Conclusions The research revealed that RNU5E-1 was down-regulated in HCC and it could be one of indicators for diagnosis and prognostic prediction of HCC patients.
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Affiliation(s)
- Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Zhongquan Sun
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Sitong Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Xin Han
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Yanjie Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Qianhui Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Liuzhi Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Hao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Yang Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Chang Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Hao Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Yao Ge
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
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Suárez-Bonnet A, Priestnall SL, Ramírez GA, Molín J, Jaber JR. Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus). J Comp Pathol 2020; 179:25-30. [PMID: 32958143 DOI: 10.1016/j.jcpa.2020.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/04/2020] [Accepted: 07/01/2020] [Indexed: 01/20/2023]
Abstract
We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms.
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Affiliation(s)
- A Suárez-Bonnet
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hatfield, UK.
| | - S L Priestnall
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hatfield, UK
| | - G A Ramírez
- Department of Animal Science, Universitat de Lleida, Lleida, Spain
| | - J Molín
- Department of Animal Science, Universitat de Lleida, Lleida, Spain
| | - J R Jaber
- Morphology Department, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain
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32
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MiR-155 and MiR-665 Role as Potential Non-invasive Biomarkers for Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection. J Transl Int Med 2020; 8:32-40. [PMID: 32435610 PMCID: PMC7227164 DOI: 10.2478/jtim-2020-0006] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and Objectives Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer associated death globally. Serum micro RNAs are full of potential as noninvasive biomarkers. Here, we aim to assess the performance of serum MicroRNA-155 and MicroRNA-665 as diagnostic biomarker for HCC comparing to AFP. Methods Serum samples were collected from 200 subjects (40 healthy control, 80 chronic hepatitis C patients with cirrhosis and without HCC (LC) and 80 HCC patients currently infected by hepatitis C infection and didn’t start the treatment). The HCC patients didn’t include alcoholic liver disease, nonalcoholic fatty liver disease nor autoimmune liver disease. MicroRNA-155 and MicroRNA-665 expression were measured by real-time quantitative PCR (RT-qPCR), while AFP level was assessed by ELISA method. Results Both miR-155 and miR-665 were significantly elevated in HCC group as compared to both control and LC groups. The comparison between LC and HCC patients revealed that the serum level of miR-155 was a significant increase in HCC patients compared to LC patients; however, the serum level of miR-665 didn’t show any significant difference between the same two groups. MiR-665 expression level showed a direct correlation with tumor size in HCC patients. Conclusions Using measurement against AFP level in serum, miR-665 is considered a promising serum biomarker for the diagnosis of HCC patients among the LC patients without HCC. MiR-155 didn’t provide a better performance than serum AFP as a diagnostic biomarker among the same group. MiR-665 may serve as a good indicator for HCC prognosis.
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33
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Omran MM, Farid K, Omar MA, Emran TM, El-Taweel FM, Tabll AA. A combination of α-fetoprotein, midkine, thioredoxin and a metabolite for predicting hepatocellular carcinoma. Ann Hepatol 2020; 19:179-185. [PMID: 31648804 DOI: 10.1016/j.aohep.2019.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 08/29/2019] [Accepted: 09/03/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND OBJECTIVES The heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection. PATIENTS/MATERIALS AND METHODS This study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography-mass spectrometry (GC-MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC. RESULTS The model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0-1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups. CONCLUSION This model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.
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Affiliation(s)
- Mohamed M Omran
- Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt.
| | - Khaled Farid
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mona A Omar
- Chemistry Department, Faculty of Science, Damietta University, New Damietta, Egypt
| | - Tarek M Emran
- Clinical Pathology Department, Faculty of Medicine, Al-Azhar University, New Damietta, Egypt
| | - Fathy M El-Taweel
- Chemistry Department, Faculty of Science, Damietta University, New Damietta, Egypt
| | - Ashraf A Tabll
- Microbial Biotechnology Department, National Research Centre, Giza, Egypt
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Zhou X, Wang J, Tang M, Huang M, Xu L, Peng Z, Li ZP, Feng ST. Hepatocellular carcinoma with hilar bile duct tumor thrombus versus hilar Cholangiocarcinoma on enhanced computed tomography: a diagnostic challenge. BMC Cancer 2020; 20:54. [PMID: 31969123 PMCID: PMC6977349 DOI: 10.1186/s12885-020-6539-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 01/13/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with hilar bile duct tumor thrombus (HBDTT) often mimic hilar cholangiocarcinoma (hilar CC). The purpose of this study is to analyze the Computed Tomography (CT) characteristics of HCC with HBDTT and to identify imaging features to aid its differentiation from hilar CC on enhanced CT. METHODS We retrospectively identified 58 cases with pathologically proved HCC with HBDTT between 2011 and 2018. Seventy-seven cases of pathologically proven hilar CCs were selected during the same period. The clinical features and CT findings of the two groups were reviewed and compared. RESULTS HCC with HBDTTs are more commonly found in men (87.9% vs 63.6%, p = 0.001) with lower age of onset (49.84 vs 58.61 years; p < 0.001) in comparison to hilar CCs. Positive correlation were identified between HCC with HBDTTs and chronic HBV infection (72.4% vs 11.7%; p < 0.001), increased serum AFP (67.2% vs 1.3%; p < 0.001), CA19-9 level (58.6% vs 85.7%; p < 0.001) and CEA level (3.4% vs 29.9%; p = 0.001), parenchymal lesion with intraductal lesion (100% vs 18.2%; p < 0.001), washout during the portal venous phase (84.5% vs 6.5%; p < 0.001), thickened bile duct wall (8.6% vs 93.5%; p < 0.001), intrahepatic vascular embolus (44.8% vs 7.8%; p < 0.001), splenomegaly (34.5% vs 2.6%, p < 0.001). A scoring system consisting of the five parameters obtained from characteristics mentioned above was trialed. The sensitivity and specificity for diagnosing HCC with HBDTT were 96.39, 100 and 92.5% respectively when the total score was 2 or more. CONCLUSIONS HCC with HBDTTs are often distinguishable from hilar CCs based on washout during portal venous phase without thickened bile duct wall. HBV infection and serum AFP level facilitate the differentiation.
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Affiliation(s)
- Xiaoqi Zhou
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Jifei Wang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Mimi Tang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Mengqi Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Ling Xu
- Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia
| | - Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
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Devcic Z, Elboraey M, Vidal L, Mody K, Harnois D, Patel T, Toskich BB. Individualized Ablation of Hepatocellular Carcinoma: Tailored Approaches across the Phenotype Spectrum. Semin Intervent Radiol 2019; 36:287-297. [PMID: 31680719 DOI: 10.1055/s-0039-1698755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ablation is now recommended by international guidelines for the definitive treatment of hepatocellular carcinoma (HCC). Extensive clinical studies have demonstrated outcomes comparable to surgical resection with shorter hospital stays, decreased costs, and improved quality of life. Successful ablation requires complete treatment of both tumor and margin while preserving critical adjacent structures. HCC exhibits highly variable presentations in both anatomic involvement and biology which have significant implications on choice of ablative therapy. There are now abundant ablation modalities and adjunctive techniques which can be used to individualize ablation and maximize curative results. This article provides a patient-centered summary of approaches to HCC ablation in the context of patient performance, hepatic reserve, tumor phenotype and biology, intra- and extrahepatic anatomy, and ablation technology.
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Affiliation(s)
- Zlatko Devcic
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
| | - Mohamed Elboraey
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
| | - Lucas Vidal
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Kabir Mody
- Division of Oncology, Mayo Clinic Florida, Jacksonville, Florida
| | - Denise Harnois
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Tushar Patel
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Beau B Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
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Ding Y, Fang A, Yan J, Duan J, Wang N, Yi Y, Shen C. Selective downregulation of distinct circRNAs in the tissues and plasma of patients with primary hepatic carcinoma. Oncol Lett 2019; 18:5255-5268. [PMID: 31612035 PMCID: PMC6781726 DOI: 10.3892/ol.2019.10908] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 09/06/2019] [Indexed: 02/07/2023] Open
Abstract
Multiple studies have indicated that circular RNAs (circRNAs) are closely associated with malignant tumor development and metastasis. However, the significance of circRNAs in primary hepatic carcinoma (PHC), particularly in the plasma, remains largely undetermined. In the current study, circRNA expression profiles in three pairs of tumor and adjacent normal samples from patients with PHC, were examined using circRNA chip screening. A total of 80 circRNAs were upregulated, while 75 circRNAs were downregulated in PHC tissues, relative to para-tumor tissues (fold change, ≥1.5). A total of two upregulated circRNAs and three downregulated circRNAs were selected as candidates for further validation of their differential expression. This was performed using reverse transcription-quantitative PCR with 11 pairs of PHC tissues and para-tumor tissues. The results indicated that hsa_circ_0003056 exhibited reduced expression in PHC tissues. Moreover, hsa_circ_0003056 and hsa_circ_0067127 were quantified in the plasma samples of 35 PHC patients and 32 healthy donors. The results revealed that hsa_circ_0067127 was significantly downregulated in the patients' plasma. Finally, a competing endogenous RNA network was constructed, which consisted of one circRNA (hsa_circ_0003056 or has_circ_0067127), five miRNAs and miRNA-targeted genes (mRNAs). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that differentially expressed (DE) genes were significantly enriched in the pathway associated with ‘regulation of the pluripotency of stem cells’ for hsa_circ_0003056, and ‘ubiquitin-mediated proteolysis’ and ‘prostate cancer’ for hsa_circ_0067127. Gene ontology analysis revealed that DE genes were primarily associated with the ‘modulation of kinase activity’ and ‘intracellular and transmembrane-ephrin receptor activity’ for hsa_circ_0003056, ‘artery morphogenesis activity’, ‘HOPS complex and transferase activity’ and in ‘transferring acyl groups’ for hsa_circ_0067127. This approach indicated that hsa_circ_0003056 in PHC tissue, and hsa_circ_0067127 in PHC plasma, are downregulated and may be implicated in the tumorigenesis of PHC.
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Affiliation(s)
- Yan Ding
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, P.R. China.,Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Anning Fang
- Department of Basic Medicine, Anhui Medical College, Hefei, Anhui 230601, P.R. China
| | - Jialai Yan
- Department of Medical Technology, Anhui Medical College, Hefei, Anhui 230601, P.R. China
| | - Jie Duan
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, P.R. China
| | - Nianyue Wang
- Department of Clinical Laboratory, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, P.R. China
| | - Yongxiang Yi
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, P.R. China
| | - Chuanlai Shen
- Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China
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Zheng W, Yao M, Fang M, Pan L, Wang L, Yang J, Dong Z, Yao D. Oncogenic Wnt3a: A Candidate Specific Marker and Novel Molecular Target for Hepatocellular Carcinoma. J Cancer 2019; 10:5862-5873. [PMID: 31737122 PMCID: PMC6843874 DOI: 10.7150/jca.31599] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/20/2019] [Indexed: 12/22/2022] Open
Abstract
Background and aim: It is of the utmost importance for the specific diagnosis and effective therapy of hepatocellular carcinoma (HCC). Abnormality of oncogenic Wingless-type MMTV integration site family member 3a (Wnt3a) has been associated with progression of HCC. In this study, we aimed to evaluate Wnt3a as a novel biomarker and target for HCC. Methods: Circulating Wnt3a levels were quantitatively detected in a cohort of chronic liver diseases by an enzyme-linked immune-absorbent assay (ELISA). Hepatic Wnt3a expression in HCC and para-cancerous tissues was analyzed by immunohistochemistry. Prognostic value of Wnt3a for HCC was discovered in the cohort from the Cancer Genome Atlas (TCGA). Dynamic alterations of Wnt3a levels were detected in the hepatocarcinogenesis model induced by 2-acetylaminofluorene. Effects of Wnt3a on biological behaviors were evaluated in vitro and in vivo based on Crispr/Cas9. Results: Up-regulated Wnt3a levels were observed in serum of HCC patients with high specificity and sensitivity for HCC diagnosis. Combination of Wnt3a and AFP could improve sensitivity to 93.9% in serological detection. In addition, Wnt3a expression in HCC tissues was significantly higher than that in para-cancerous tissues. The cohort of TCGA demonstrated that high Wnt3a expression led to a poor survival of HCC patients, especially in cases at advanced stages. Furthermore, the hepatocarcinogenesis model showed that Wnt3a dynamically increased in the development of HCC. Functionally, silencing Wnt3a by Crispr/Cas9 suppressed the proliferation, colony formation, induced cell cycle arrest of HCC cells by de-activating Wnt/β-catenin pathway in vitro, and inhibited xenograft tumor growth in vivo. Conclusions: Oncogenic Wnt3a could be considered as a candidate biomarker and novel target for HCC.
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Affiliation(s)
- Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Miao Fang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Liuhong Pan
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Dengfu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Rice A, Del Rio Hernandez A. The Mutational Landscape of Pancreatic and Liver Cancers, as Represented by Circulating Tumor DNA. Front Oncol 2019; 9:952. [PMID: 31608239 PMCID: PMC6769086 DOI: 10.3389/fonc.2019.00952] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 09/09/2019] [Indexed: 02/06/2023] Open
Abstract
The mutational landscapes of pancreatic and liver cancers share many common genetic alterations which drive cancer progression. However, these mutations do not occur in all cases of these diseases, and this tumoral heterogeneity impedes diagnosis, prognosis, and therapeutic development. One minimally invasive method for the evaluation of tumor mutations is the analysis of circulating tumor DNA (ctDNA), released through apoptosis, necrosis, and active secretion by tumor cells into various body fluids. By observing mutations in those genes which promote transformation by controlling the cell cycle and oncogenic signaling pathways, a representation of the mutational profile of the tumor is revealed. The analysis of ctDNA is a promising technique for investigating these two gastrointestinal cancers, as many studies have reported on the accuracy of ctDNA assessment for diagnosis and prognosis using a variety of techniques.
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Affiliation(s)
- Alistair Rice
- Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London, United Kingdom
| | - Armando Del Rio Hernandez
- Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London, United Kingdom
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Xiao K, Tian Z. GPSeeker Enables Quantitative Structural N-Glycoproteomics for Site- and Structure-Specific Characterization of Differentially Expressed N-Glycosylation in Hepatocellular Carcinoma. J Proteome Res 2019; 18:2885-2895. [DOI: 10.1021/acs.jproteome.9b00191] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Kaijie Xiao
- School of Chemical Science & Engineering and Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai 200092, China
| | - Zhixin Tian
- School of Chemical Science & Engineering and Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai 200092, China
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40
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Wu JS, Feng JL, Zhu RD, Liu SG, Zhao DW, Li N. Histopathological characteristics of needle core biopsy and surgical specimens from patients with solitary hepatocellular carcinoma or intrahepatic cholangiocarcinoma. World J Gastrointest Oncol 2019; 11:404-415. [PMID: 31139310 PMCID: PMC6522762 DOI: 10.4251/wjgo.v11.i5.404] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/29/2019] [Accepted: 04/19/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pathological manifestations of hepatic tumours are often associated with prognosis. Although surgical specimens (SS) can provide more information, currently, pre-treatment needle core biopsy (NCB) is increasingly showing important value in understanding the nature of liver tumors and even in diagnosis and treatment decisions. However, the concordance of the clinicopathological characteristics and immunohistochemical (IHC) staining between NCB and SS from patients with hepatic tumours were less concerned.
AIM To introduce a more accurate method for interpreting the IHC staining results in order to improve the diagnostic value of hepatic malignancy in NCB samples.
METHOD A total of 208 patients who underwent both preoperative NCB and surgical resection for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between 2008 and 2015 were enrolled in this study. The expression of CK19, GPC3, and HepPar1 were detected by IHC staining. Clinicopathological, NCB, and surgical data were collected and analysed using χ2 and kappa statistics.
RESULTS Morphologically, the presence of compact tumour nests or a cord-like structure in NCB was considered the primary cause of misdiagnosis of HCC from ICC. The kappa statistic showed a moderate agreement in histomorphology (k = 0.504) and histological grade (k = 0.488) between NCB and SS of the tumours. A 4-tier (+++, ++, +, and -) scoring scheme that emphasized the focal neoplastic cell immunoreactivity of tumour cells revealed perfect concordance of CK19, GPC3 and HepPar1 between NCB and SS (k = 0.717; k = 0.768; k = 0.633). Furthermore, with the aid of a binary classification derived from the 4-tier score, a high concordance was achieved in interpreting the IHC staining of the three markers between NCB and final SS (k = 0.931; k = 0.907; k = 0.803), increasing the accuracy of NCB diagnosis C (k = 0.987; area under the curve = 0.997, 95%CI: 0.990-1.000; P < 0.001).
CONCLUSION These findings imply that reasonable interpretation of IHC results in NCB is vital for improving the accuracy of tumour diagnosis. The simplified binary classification provides an easy and applicable approach.
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Affiliation(s)
- Ju-Shan Wu
- General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Ji-Liang Feng
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Rui-Dong Zhu
- General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - San-Guang Liu
- Department of Hepatobiliary Surgery, the Second Hospital, Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Da-Wei Zhao
- Medical Imaging Department, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Ning Li
- General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
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Teufel M, Seidel H, Köchert K, Meinhardt G, Finn RS, Llovet JM, Bruix J. Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma. Gastroenterology 2019; 156:1731-1741. [PMID: 30738047 DOI: 10.1053/j.gastro.2019.01.261] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 01/28/2019] [Accepted: 01/30/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS In a phase 3 trial (RESORCE), regorafenib increased overall survival compared with placebo in patients with hepatocellular carcinoma (HCC) previously treated with sorafenib. In an exploratory study, we analyzed plasma and tumor samples from study participants to identify genetic, microRNA (miRNA), and protein biomarkers associated with response to regorafenib. METHODS We obtained archived tumor tissues and baseline plasma samples from patients with HCC given regorafenib in the RESORCE trial. Baseline plasma samples from 499 patients were analyzed for expression of 294 proteins (DiscoveryMAP) and plasma samples from 349 patients were analyzed for levels of 750 miRNAs (miRCURY miRNA PCR). Tumor tissues from 7 responders and 10 patients who did not respond (progressors) were analyzed by next-generation sequencing (FoundationOne). Forty-six tumor tissues were analyzed for expression patterns of 770 genes involved in oncogenic and inflammatory pathways (PanCancer Immune Profiling). Associations between plasma levels of proteins and miRNAs and response to treatment (overall survival and time to progression) were evaluated using a Cox proportional hazards model. RESULTS Decreased baseline plasma concentrations of 5 of 266 evaluable proteins (angiopoietin 1, cystatin B, the latency-associated peptide of transforming growth factor beta 1, oxidized low-density lipoprotein receptor 1, and C-C motif chemokine ligand 3; adjusted P ≤ .05) were significantly associated with increased overall survival time after regorafenib treatment. Levels of these 5 proteins, which have roles in inflammation and/or HCC pathogenesis, were not associated with survival independently of treatment. Only 20 of 499 patients had high levels and a reduced survival time. Plasma levels of α-fetoprotein and c-MET were associated with poor outcome (overall survival) independently of regorafenib treatment only. We identified 9 plasma miRNAs (MIR30A, MIR122, MIR125B, MIR200A, MIR374B, MIR15B, MIR107, MIR320, and MIR645) whose levels significantly associated with overall survival time with regorafenib (adjusted P ≤ .05). Functional analyses of these miRNAs indicated that their expression level associated with increased overall survival of patients with tumors of the Hoshida S3 subtype. Next-generation sequencing analyses of tumor tissues revealed 49 variants in 27 oncogenes or tumor suppressor genes. Mutations in CTNNB1 were detected in 3 of 10 progressors and VEGFA amplification in 1 of 7 responders. CONCLUSION We identified expression patterns of plasma proteins and miRNAs that associated with increased overall survival times of patients with HCC following treatment with regorafenib in the RESORCE trial. Levels of these circulating biomarkers and genetic features of tumors might be used to identify patients with HCC most likely to respond to regorafenib. ClinicalTrials.gov number NCT01774344. NCBI GEO accession numbers: mRNA data (NanoString): GSE119220; miRNA data (Exiqon): GSE119221.
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Affiliation(s)
| | | | | | | | - Richard S Finn
- David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Josep M Llovet
- BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain; Liver Cancer Program, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
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42
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Lun Y, Sun J. [Identification of differentially expressed genes in peripheral blood mononuclear cells of patients with hepatocellular carcinoma and its regulatory network analysis]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2019; 48:148-157. [PMID: 31309752 PMCID: PMC8800654 DOI: 10.3785/j.issn.1008-9292.2019.04.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 04/15/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVE To identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to analyze their regulatory network. METHODS The DEGs in PBMCs of HCC patients were screened based on GEO database. The functional enrichment analysis and interaction analysis were carried out for DEGs. MCODE algorithm was used to screen core genes of DEGs, and the mirDIP and starBase online tools were used to predict upstream miRNAs and lncRNAs of the core genes. RESULTS A total of 265 DEGs with a high credibility were identified, which were mainly enriched in the biological activity, such as regulation of cell proliferation, metabolic regulation, cell communication and signaling, and inflammatory diseases according to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the two analyses were correlated. Four diagnostic candidate genes were identified, including FUS RNA binding protein, C-X-C motif chemokine ligand 8, cullin 1 and RNA polymerase Ⅱ subunit H. Subsequently, 10 miRNAs, 1 lncRNAs and 38 circRNAs were predicted, and finally a lncRNA/circRNA-miRNA-mRNA-pathway regulatory networks was constructed. CONCLUSIONS The diagnostic candidate genes and its regulatory network in HCC PBMC have been identified based on data mining, which could provide potential tumor biomarkers for early diagnosis and treatment of HCC.
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Affiliation(s)
- Yongzhi Lun
- Department of Laboratory Medicine, School of Pharmacy and Medical Technology, Putian University, Putian 351100, Fujian Province, China
| | - Jie Sun
- Department of Laboratory Medicine, School of Pharmacy and Medical Technology, Putian University, Putian 351100, Fujian Province, China
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Madduru D, Ijaq J, Dhar S, Sarkar S, Poondla N, Das PS, Vasquez S, Suravajhala P. Systems Challenges of Hepatic Carcinomas: A Review. J Clin Exp Hepatol 2019; 9:233-244. [PMID: 31024206 PMCID: PMC6477144 DOI: 10.1016/j.jceh.2018.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 05/10/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular Carcinoma (HCC) is ubiquitous in its prevalence in most of the developing countries. In the era of systems biology, multi-omics has evinced an extensive approach to define the underlying mechanism of disease progression. HCC is a multifactorial disease and the investigation of progression of liver cirrhosis becomes much extensive with cultivating omics approaches. We have performed a comprehensive review about such challenges in multi-omics approaches that are concerned to identify the immunological, genetics and epidemiological factors associated with HCC.
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Affiliation(s)
- Dhatri Madduru
- Department of Biochemistry, Osmania University, Hyderabad 500007, TG, India
- Bioclues.org
| | - Johny Ijaq
- Department of Genetics and Biotechnology, Osmania University, Hyderabad 500007, TG, India
- Bioclues.org
| | | | | | | | - Partha S. Das
- Bioclues.org
- Patient MD, Chicago, IL 60640-5710, United States
| | - Silvia Vasquez
- Bioclues.org
- Instituto Peruano de Energía Nuclear, Avenida Canadá 1470, Lima, Peru
| | - Prashanth Suravajhala
- Bioclues.org
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Statue Circle 302001, RJ, India
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Arnaiz E, Sole C, Manterola L, Iparraguirre L, Otaegui D, Lawrie CH. CircRNAs and cancer: Biomarkers and master regulators. Semin Cancer Biol 2018; 58:90-99. [PMID: 30550956 DOI: 10.1016/j.semcancer.2018.12.002] [Citation(s) in RCA: 300] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 11/30/2018] [Accepted: 12/10/2018] [Indexed: 02/06/2023]
Abstract
Circular RNAs (circRNAs) are a novel class of regulatory RNAs that despite being relatively abundant have only recently begun to be explored. There are many thousands of genes that appear capable of producing circRNAs, however the function of all but a handful remain to be determined. What is emerging about these highly conserved molecules is that they play important roles in biology and cancer biology in particular. The most explored function of circRNAs is as master regulators of gene expression that act to sequester or ´sponge´ other gene expression regulators, in particular miRNAs. They have also been demonstrated to function via direct modulation of transcription, and by interfering with splicing mechanisms. Although generally expressed in low abundance when compared to their linear counterparts, they are often expressed in a tissue- and developmental stage- specific manner. Coupled with their remarkable resistance to RNAse activity due to a covalent closed cyclic structure, circRNAs show great promise as novel biomarkers of cancer and other diseases. In this review we consider the current state of knowledge regarding these molecules, their synthesis, function, and association with cancer. We will also review some of the challenges that remain to be resolved if this emerging class of RNAs are really to become useful in the clinic.
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Affiliation(s)
- Esther Arnaiz
- Molecular Oncology Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain
| | - Carla Sole
- Molecular Oncology Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain
| | - Lorea Manterola
- Molecular Oncology Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain
| | - Leire Iparraguirre
- Multiple Sclerosis Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain
| | - David Otaegui
- Multiple Sclerosis Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain
| | - Charles H Lawrie
- Molecular Oncology Group, Biodonostia Research Institute, Paseo Doctor Begiristain, s/n San Sebastián, 20014, Spain; Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; IKERBASQUE, Basque Foundation for Science, María Díaz Haroko Kalea, 3, 48013, Bilbao, Spain.
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45
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Kato A, Naitoh I, Miyabe K, Hayashi K, Yoshida M, Hori Y, Natsume M, Jinno N, Asano G, Kato H, Kuno T, Takahashi S, Kataoka H. An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma. Dig Dis Sci 2018; 63:3376-3381. [PMID: 30206756 DOI: 10.1007/s10620-018-5280-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 09/07/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND The ability of fluorescence in situ hybridization (FISH) assays in endoscopic transpapillary bile duct biopsy specimens to predict the prognosis of cholangiocarcinoma (CCA) has not been elucidated. AIMS We aimed to clarify the association between the results of UroVysion FISH assays and the prognosis of CCA. METHODS We retrospectively reviewed 49 specimens obtained by transpapillary forceps biopsy from consecutive patients with CCA. The copy numbers of chromosomes 3, 7, and 17 were evaluated by FISH assay using UroVysion. We compared the overall survival (OS) of CCA patients with and without increased copy numbers of chromosomes 3, 7, and 17. Furthermore, we evaluated the association between OS and the clinicopathological parameters of CCA patients. RESULTS The OS was significantly shorter in patients with than without an increased chromosome 7 copy number (log-rank p = 0.015; median OS 11.9 vs. 20.7 months). In the univariate analyses, age (p = 0.012), ECOG performance status (p = 0.046), tumor stage (p = 0.046), surgery (p = 0.006), and an increased chromosome 7 copy number (p = 0.017) were significantly associated with OS. The multivariate analysis revealed that an increased chromosome 7 copy number (hazard ratio, 2.46; 95% CI 1.15-5.27; p = 0.021) and advanced clinical stage (hazard ratio, 2.26; 95% CI 1.11-4.63; p = 0.025) were independently predictive of a poor OS. CONCLUSIONS Detection by FISH assay of an increased chromosome 7 copy number in transpapillary forceps biopsy specimens is predictive of a poor prognosis in CCA patients.
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Affiliation(s)
- Akihisa Kato
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
| | - Katsuyuki Miyabe
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Kazuki Hayashi
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Michihiro Yoshida
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Yasuki Hori
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Makoto Natsume
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Naruomi Jinno
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Go Asano
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
| | - Hiroyuki Kato
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Toshiya Kuno
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
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Jeong WK, Jamshidi N, Felker ER, Raman SS, Lu DS. Radiomics and radiogenomics of primary liver cancers. Clin Mol Hepatol 2018; 25:21-29. [PMID: 30441889 PMCID: PMC6435966 DOI: 10.3350/cmh.2018.1007] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/16/2018] [Indexed: 02/07/2023] Open
Abstract
Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.
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Affiliation(s)
- Woo Kyoung Jeong
- Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.,Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Neema Jamshidi
- Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Ely Richard Felker
- Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Steven Satish Raman
- Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - David Shinkuo Lu
- Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
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Ma J, Hou Y, Xia J, Zhu X, Wang ZP. Tumor suppressive role of rottlerin in cancer therapy. Am J Transl Res 2018; 10:3345-3356. [PMID: 30662591 PMCID: PMC6291697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 10/10/2018] [Indexed: 06/09/2023]
Abstract
Cancer as a major public health problem is a big trouble to be cured at present in the world. Thus, it is essential to discover better anticancer drugs to treat cancer patients. It has been reported that rottlerin, a natural polyphenolic compound from the mature fruits of Mallotus philippinensis, possesses multiple anti-cancer biological activities. Rottlerin exhibited its antitumor property in a variety of human cancers, suggesting that rottlerin could be a potential agent for treating cancers. In this review we discuss the recent literature regarding the biological functions and tumor suppressive mechanisms of rottlerin in cancers. We hope rottlerin will be further exploited for potential treatment of human cancers.
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Affiliation(s)
- Jia Ma
- Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical CollegeBengbu 233030, Anhui, China
| | - Yingying Hou
- Chinese Academy of Sciences Shanghai Institute of Materia MedicaShanghai 201203, China
| | - Jun Xia
- Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical CollegeBengbu 233030, Anhui, China
| | - Xueqiong Zhu
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China
| | - Z Peter Wang
- Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical CollegeBengbu 233030, Anhui, China
- Center of Scientific Research, The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBoston, MA, USA
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De Stefano F, Chacon E, Turcios L, Marti F, Gedaly R. Novel biomarkers in hepatocellular carcinoma. Dig Liver Dis 2018; 50:1115-1123. [PMID: 30217732 DOI: 10.1016/j.dld.2018.08.019] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 08/09/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths and the fifth most common cancer worldwide. Most of these patients are seen with advanced disease at the time of presentation. In spite of its high prevalence, there are not many therapeutic options available for patients with advanced-stage HCC. There is an urgent need for improving early detection and prognostication of patients with HCC. In addition, the development of new therapies targeting specific pathways involved in the pathogenesis of HCC should be a major goal for future research, with the objective of improving outcomes of patients with HCC. Biomarkers represent a relatively easy and noninvasive way to detect and estimate disease prognosis. In spite of the numerous efforts to find molecules as possible biomarkers, there is not a single ideal marker in HCC. Many new findings have shown promising results both in diagnosing and treating HCC. In this review, we summarized the most recent and relevant biomarkers in HCC.
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Affiliation(s)
- Felice De Stefano
- Transplant and Hepatobiliary Center, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, United States
| | - Eduardo Chacon
- Transplant and Hepatobiliary Center, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, United States
| | - Lilia Turcios
- Transplant and Hepatobiliary Center, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, United States
| | - Francesc Marti
- Transplant and Hepatobiliary Center, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, United States
| | - Roberto Gedaly
- Transplant and Hepatobiliary Center, Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, United States.
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Rastogi A. Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma. World J Gastroenterol 2018; 24:4000-4013. [PMID: 30254404 PMCID: PMC6148422 DOI: 10.3748/wjg.v24.i35.4000] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/23/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.
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Affiliation(s)
- Archana Rastogi
- Department of Pathology, Institute of Liver & Biliary Sciences, New Delhi 110070, India
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Huang Y, Shen Q, Bai HX, Wu J, Ma C, Shang Q, Hunt SJ, Karakousis G, Zhang PJ, Zhang Z. Comparison of Radiofrequency Ablation and Hepatic Resection for the Treatment of Hepatocellular Carcinoma 2 cm or Less. J Vasc Interv Radiol 2018; 29:1218-1225.e2. [DOI: 10.1016/j.jvir.2018.04.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 04/14/2018] [Accepted: 04/16/2018] [Indexed: 12/16/2022] Open
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