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Xin L, Zou YH, Liu CX, Lu H, Fan LJ, Xu HS, Zhou Q, Liu J, Yue ZQ, Gan JH. Methionine restriction promotes cisplatin sensitivity of gastric cancer resistant cells by down-regulating circ-CDK13 level. Exp Cell Res 2024; 443:114315. [PMID: 39488295 DOI: 10.1016/j.yexcr.2024.114315] [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: 08/05/2024] [Revised: 10/16/2024] [Accepted: 10/29/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Methionine restriction (MR) is a research direction in the treatment of gastric cancer (GC). The aim of this study was to investigate the molecular mechanism of MR on enhancing cisplatin (DDP) sensitivity of drug-resistant GC cells. METHODS Twenty pairs of GC tissues and adjacent normal gastric mucosa tissues were collected. DDP-resistant cell lines (KATO/DDP and MKN45/DDP), mouse model of GC and GC patient-derived organoid (PDO) models were established. Lentivirus-mediated METase overexpression was used for MR. Cell viability and apoptosis were detected by MTT assay and flow cytometry. Western blotting was used to detect multi-drug resistance-1 (MDR1), MDR-associated protein 1 (MRP1) eukaryotic initiation factor 4A-Ⅲ (EIF4A3), and METase protein expressions. The levels of circRNAs were detected by qRT-PCR. Tumor volume and weight were measured. The proliferation of tumor cells was detected by immunohistochemical staining. RESULTS The differentially expressed circRNAs of GC were screened in Gene Expression Omnibus database. MR in KATO/DDP and MKN45/DDP cells significantly down-regulated circ-CDK13 level. Overexpression of circ-CDK13 significantly inhibited apoptosis of sensitive cells (KATO III and MKN45). Interference with circ-CDK13 significantly promoted apoptosis of drug-resistant cells (KATO/DDP and MKN45/DDP). MR enhanced the DDP sensitivity of GC resistant cells, GC PDO and GC mice by down-regulating circ-CDK13. EIF4A3 binds to the downstream flanking sequence of circ-CDK13, and interference with EIF4A3 reduces circ-CDK13 levels, but does not affect CDK13. The expressions of circ-CDK13 and EIF4A3 in GC clinical samples were increased and positively correlated. Simultaneously overexpression of METase and EIF4A3 in resistant cells inhibited apoptosis, and further interference with circ-CDK13 reversed this effect. CONCLUSION MR inhibits circ-CDK13 level by down-regulating EIF4A3, thereby increasing the sensitivity of GC drug-resistant cells to DDP.
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Affiliation(s)
- Lin Xin
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
| | - Yong-Hui Zou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Chen-Xi Liu
- Excellent Ophthalmology Class 221, School of Ophthalmology & Optometry, Nanchang University, China
| | - Hao Lu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Luo-Jun Fan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - He-Song Xu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Qi Zhou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Jiang Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Zhen-Qi Yue
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Jin-Heng Gan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
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Zeng Q, Wang S, Bai Z, Nie Y, Xu L, Chang D. Platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with gastric cancer undergoing radical resection. Front Oncol 2024; 14:1279011. [PMID: 38511137 PMCID: PMC10951101 DOI: 10.3389/fonc.2024.1279011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 02/22/2024] [Indexed: 03/22/2024] Open
Abstract
Background Amounting literatures have reported the significance of systemic inflammatory markers for evaluating tumor prognosis. But few studies have systematically compared their superiority and their impact on adjuvant chemotherapy. Aims We aimed to investigate the ability of inflammatory markers to predict the efficacy of chemotherapy in GC patients undergoing radical therapy and to identify an effective methodology based on the study's findings that would enable clinicians to differentiate between chemotherapy-responsive populations. Methods We retrospectively enrolled 730 GC patients who underwent radical gastrectomy. Fibrinogen (FIB), platelet-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and lymph node ratio (LNR) were grouped according to cutoff values. Their clinical significance for GC prognosis was determined by multivariate COX regression analysis in the 730 GC patients and high/low PLR status subgroups. Cases were divided into four groups according to PLR status and adjuvant chemotherapy status and survival was compared among groups. Results Multivariate analysis showed that PLR was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) of GC patients. Adjuvant chemotherapy improved survival more significantly in patients with low PLR than that with high PLR. Among patients receiving adjuvant chemotherapy, low PLR was significantly associated with prolonged survival in TNM stage II, but not in TNM stage III. Conclusion Preoperative high PLR is an independent risk factor for GC patients undergoing radical gastrectomy and adversely affects the postoperative chemotherapy effect.
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Affiliation(s)
| | | | | | | | | | - Dongmin Chang
- Department of Oncology Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Wen F, Zhao F, Huang W, Liang Y, Sun R, Lin Y, Zhang W. A novel ferroptosis-related gene signature for overall survival prediction in patients with gastric cancer. Sci Rep 2024; 14:4422. [PMID: 38388534 PMCID: PMC10883968 DOI: 10.1038/s41598-024-53515-0] [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] [Accepted: 02/01/2024] [Indexed: 02/24/2024] Open
Abstract
The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient's prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.
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Affiliation(s)
- Fang Wen
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Fan Zhao
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Wenjie Huang
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China
| | - Yan Liang
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Ruolan Sun
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Yize Lin
- Clinical Laboratory Department, Hospital of the Office of the People's Government of the Tibet Autonomous Region in Chengdu, Chengdu, 850015, Sichuan, China
| | - Weihua Zhang
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
- College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
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Wang R, Zhang G, Zhu X, Xu Y, Cao N, Li Z, Han C, Qin M, Shen Y, Dong J, Ma F, Zhao A. Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer. Cancers (Basel) 2023; 15:5759. [PMID: 38136305 PMCID: PMC10741692 DOI: 10.3390/cancers15245759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/16/2023] [Accepted: 11/27/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. METHODS The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II-III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. RESULTS LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28-5.14, p = 0.008). The Kaplan-Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10-0.93, p = 0.042). CONCLUSIONS LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.
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Affiliation(s)
- Rui Wang
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
- Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Guangtao Zhang
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Xiaohong Zhu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Yan Xu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Nida Cao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Zhaoyan Li
- Department of Traditional Chinese Medicine, School of Medicine Affiliated Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China
| | - Chen Han
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Mengmeng Qin
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Yumiao Shen
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Jiahuan Dong
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Fangqi Ma
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
| | - Aiguang Zhao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; (R.W.); (G.Z.); (X.Z.); (Y.X.); (N.C.)
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Gou M, Zhang Y. Pretreatment platelet-to-lymphocyte ratio (PLR) as a prognosticating indicator for gastric cancer patients receiving immunotherapy. Discov Oncol 2022; 13:118. [PMID: 36326905 PMCID: PMC9633881 DOI: 10.1007/s12672-022-00571-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 09/27/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Previous investigations suggest that systemic inflammation markers are able to provide prognostic value in several cancers. This study seeks to characterize the ability of pretreatment platelet-to-lymphocyte ratio (PLR) to prognosticate advanced or metastatic gastric cancer patients (AGC or MGC, respectively) receiving immunotherapy. METHODS AGC and MGC patients exposed to PD-1 inhibitors from January 2016-August 2021 in the Chinese PLA General Hospital were recruited. Correlations between PLR and overall survival (OS), progression-free survival (PFS), and immunotherapy-associated tumor response rates were determined. RESULTS 237 patients were enrolled for this retrospective investigation. The 6 month and 12 month PFS based on the area under the curve value was 0.60 and 0.65 (p < 0.05). based on a calculated PLR cut-off value of 139.41, The PLR < 139.41 group has a longer OS in contrast with the PLR ≥ 139.41 group (13.46 m vs 10.71 m, HR = 0.57, 95% CI 0.42-0.78, p = 0.004). The PLR < 139.41 group had a PFS of 7.93 m in contrast to the 4.75 m seen in those with PLR ≥ 139.41 group (HR = 0.57, 95% CI 0.43-0.76, p = 0.002). The disease control rate (DCR) and objective response rate (ORR) were 86.17% and 30.85%, respectively, in the PLR < 139.41 group, but were 82.52% and 32.17%, respectively in the PLR ≥ 139.41 group. Both groups did not show any marked differences in terms of ORR and DCR (p = 0.887, p = 0.476). PLR is an independent prognostic indicator for OS and PFS upon uni- and multivariate analyses (p < 0.05). CONCLUSIONS Pre-treatment PLR correlated significantly with PFS and OS in AGC and MGC patients who received immunotherapy. An elevated PLR may provide guidance on subsequent treatment options.
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Affiliation(s)
- Miaomiao Gou
- Medical Oncology Department, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yong Zhang
- Medical Oncology Department, The Second Medical Center, Chinese PLA General Hospital, Fuxing road 28, Haidian district, Beijing, 100853 People’s Republic of China
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Li YT, Zhou XS, Han XM, Tian J, Qin Y, Zhang T, Liu JL. Pretreatment serum albumin-to-alkaline phosphatase ratio is an independent prognosticator of survival in patients with metastatic gastric cancer. World J Gastrointest Oncol 2022; 14:1002-1013. [PMID: 35646278 PMCID: PMC9124991 DOI: 10.4251/wjgo.v14.i5.1002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/26/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Previous studies have suggested that a low albumin-to-alkaline phosphatase ratio (AAPR) is associated with a lower survival rate in patients with various malignancies. However, the relationship between pretreatment AAPR and the prognosis of patients with gastric cancer (GC) remains unclear.
AIM To investigate the prognostic value of AAPR in distant metastatic GC.
METHODS A total of 191 patients with distant metastatic cancer from a single institute were enrolled in this study. Pretreatment clinical data, including serum albumin and alkaline phosphatase levels, were collected. A chi-square test or Fisher’s exact test was applied to evaluate the correlations between AAPR and various clinical parameters in GC patients. The Kaplan–Meier method and Cox proportional hazards regression model were used to evaluate the prognostic efficacy of AAPR in metastatic GC patients. A two-sided P value lower than 0.05 was considered statistically significant.
RESULTS A receiver operating characteristic curve indicated that 0.48 was the optimal threshold value for AAPR. AAPR ≤ 0.48 was significantly associated with bone (P < 0.05) and liver metastasis (P < 0.05). Patients with high levels of AAPR had better survival in terms of overall survival (OS) and progression-free survival (PFS), regardless of the presence of liver/bone metastasis. Pretreatment AAPR was found to be a favorable predictor of OS and PFS based on a multivariate cox regression model. AAPR-M system, constructed based on AAPR and number of metastatic sites, showed superior predictive ability relative to the number of metastatic sites for predicting survival.
CONCLUSION Pretreatment AAPR may serve as an independent prognostic factor for predicting PFS and OS in patients with metastatic GC. Furthermore, AAPR may assist clinicians with individualizing treatment.
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Affiliation(s)
- Yu-Ting Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiao-Shu Zhou
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiao-Ming Han
- Department of Ultrasound Medicine, Jingmen Second People’s Hospital, Jingchu University of Technology Affiliated Central Hospital, Jingmen 448000, Hubei Province, China
| | - Jing Tian
- Department of Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - You Qin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Jun-Li Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Hu G, Wang S, Wang S, Huang L. Elevated baseline circulating platelet-to-lymphocyte ratio and survival in initial stage Ⅳ gastric cancer patients: A meta-analysis. PLoS One 2022; 17:e0265897. [PMID: 35436305 PMCID: PMC9015147 DOI: 10.1371/journal.pone.0265897] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 03/09/2022] [Indexed: 12/22/2022] Open
Abstract
Background Systemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of baseline circulating platelet–to–lymphocyte ratio (PLR) (known as a marker of SIR) in human initial stage Ⅳ gastric cancer (GC) remains controversial. Hence, we performed this meta-analysis to assess the value of it in prognosis prediction for these patients. Materials and methods We searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0. Results A total of 3025 patients with initial stage Ⅳ GC from 13 published studies were incorporated into this meta-analysis. We found that elevated baseline circulating PLR was significantly associated with decreased overall survival (OS), but not with progression–free survival (PFS) in stage Ⅳ GC patients. However, in stratified analyses, high PLR was only associated with worse 1-year and 2-year OS, but not with 3-year or 4-year OS; In addition, it was considerably related with reduced 6-month PFS, but not with 1-year or 2-year PFS. Moreover, high PLR markedly correlated with peritoneal metastasis of GC. Conclusion Elevated baseline circulating PLR decreased 1-year OS and 6-month PFS in initial stage Ⅳ GC patients, implicating that it is a valuable prognostic index for these patients and modifying the inflammatory responses may have a potential for effective treatment.
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Affiliation(s)
- Guoming Hu
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang, China
- * E-mail: (GH); (LH)
| | - Shimin Wang
- Department of Nephrology, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang, China
| | - Songxiang Wang
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang, China
| | - Liming Huang
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang, China
- * E-mail: (GH); (LH)
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Peng X, Zeng W, Tang B, He A, Zhang M, Luo R. Utility of Pretreatment Blood Platelet-To-Lymphocyte Ratio in Prediction of Clinical Outcomes and Chemosensitivity in Patients with Advanced Gastric Cancer: A Meta-Analysis. MEDICAL SCIENCE MONITOR : INTERNATIONAL MEDICAL JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2022; 28:e933449. [PMID: 35095093 PMCID: PMC8815280 DOI: 10.12659/msm.933449] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background The results of previous studies that evaluated the association between pretreatment blood platelet-to-lymphocyte ratio (PLR) and clinical outcomes and chemosensitivity in patients with advanced gastric cancer are inconsistent. Therefore, this study was designed to investigate the association between pretreatment blood PLR and clinical outcomes and chemosensitivity in advanced gastric cancer patients. Material/Methods We performed a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library up to Mar 9, 2021. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were pooled for meta-analysis. The quality of the included studies was measured by the Newcastle-Ottawa Quality Assessment Scale. Results We included 17 studies comprising 3499 patients with advanced GC in this meta-analysis. Pooled results demonstrated that high PLR was correlated with poor OS (HR=1.429, 95% CI=1.246–1.639, P<0.001) and DFS (HR=1.47, 95% CI=1.14–1.88, P=0.003) compared with low PLR in patients with advanced GC. Moreover, high PLR was associated with a lower response to chemotherapy in patients with advanced GC (OR=1.395, 95% CI=1.056–1.841, P=0.019). However, there was no significant correlation between PLR and clinicopathological features. Conclusions This meta-analysis suggests that high PLR is a risk factor for unfavorable OS, DFS, and chemosensitivity in patients with advanced GC.
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Affiliation(s)
- Xiulan Peng
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, China (mainland)
| | - Wei Zeng
- Department of Neurology, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, China (mainland)
| | - Bing Tang
- Department of Orthopedics, Dongfeng Hospital Affiliated to Hubei University of Medicine, Shiyan, Hubei, China (mainland)
| | - Anbing He
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, China (mainland)
| | - Min Zhang
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan, Hubei, China (mainland)
| | - Renfeng Luo
- Department of Diagnostics, Jianghan University, Wuhan, Hubei, China (mainland)
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Jia T, Zhang R, Kong F, Zhang Q, Xi Z. The Prognostic Role and Nomogram Establishment of a Novel Prognostic Score Combining with Fibrinogen and Albumin Levels in Patients with WHO Grade II/III Gliomas. Int J Gen Med 2021; 14:2137-2145. [PMID: 34093034 PMCID: PMC8169085 DOI: 10.2147/ijgm.s303733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/14/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose World Health Organization (WHO) Grades II and III gliomas [also known as low grade gliomas (LGGs)] displayed different malignant behaviors and survival outcomes compared to Grade IV gliomas. This study aimed to identify the prognostic predictive value of a novel cumulative prognostic score [combined with fibrinogen and albumin levels (FA score)], establish and validate a point-based nomogram in LGG patients. Patients and Methods A total of 91 patients who underwent total glioma resection at Shengjing Hospital of China Medical University between 2011 and 2013 were enrolled to establish a prognostic nomogram. All patients were histologically diagnosed as grades II/III, and never received radiotherapy or chemotherapy before surgery. Data collection included patient characteristics, clinicopathological factors, and preoperative hematology results. The performance of the nomogram was subsequently validated by the concordance index (c-index), calibration curve, and receiver operating characteristic (ROC) curve. Results The FA score was negatively associated with the overall survival (OS) of LGG patients (p < 0.001). The results of multivariate analysis showed that FA score [p = 0.006, HR = 1.92, 95% confidence interval (CI): 1.21–3.05], age (p = 0.002, HR = 3.014, 95% CI:1.52–5.97), and white blood count (p < 0.001, HR = 4.24, 95% CI: 2.08–8.67) were independent prognostic factors for overall survival (OS). The study established a nomogram to predict OS with a c-index of 0.783 (95% CI, 0.72–0.84). Conclusion FA score might be a potential prognostic biomarker for LGG patients, and a reliable point-based nomogram will help clinicians to decide on the best treatment plans.
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Affiliation(s)
- Tianshu Jia
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Rui Zhang
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Fanfei Kong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Qianjiao Zhang
- Pain Department, The People's Hospital of Liaoning Province, Shenyang, People's Republic of China
| | - Zhuo Xi
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
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Catanese S, Aringhieri G, Vivaldi C, Salani F, Vitali S, Pecora I, Massa V, Lencioni M, Vasile E, Tintori R, Balducci F, Falcone A, Cappelli C, Fornaro L. Role of Baseline Computed-Tomography-Evaluated Body Composition in Predicting Outcome and Toxicity from First-Line Therapy in Advanced Gastric Cancer Patients. J Clin Med 2021; 10:jcm10051079. [PMID: 33807648 PMCID: PMC7961444 DOI: 10.3390/jcm10051079] [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: 02/01/2021] [Revised: 02/22/2021] [Accepted: 02/26/2021] [Indexed: 01/06/2023] Open
Abstract
Sarcopenia is recognised as a predictor of toxicity and survival in localised and locally advanced gastric cancer (GC). Its prognostication power in advanced unresectable or metastatic GC (aGC) is debated. The survival impact of visceral and subcutaneous fat distribution (visceral fat area (VFA)/subcutaneous fat area (SFA)) is ambiguous. Our aim was to determine the influence of body composition parameters (BCp) on toxicity and survival in aGC patients undergoing palliative treatment. BCp were retrospectively assessed by baseline computed tomography for 78 aGC patients who received first-line chemotherapy from March 2010 to January 2017. Correlations between BCp and toxicity and survival were calculated by χ2-test and by log-rank-test and Cox-model, respectively. Sarcopenia fails to show association with progression-free survival (PFS) (p = 0.44) and overall survival (OS) (p = 0.88). However, sarcopenia influences the development of high-grade neutropenia (p = 0.048) and mucositis (p = 0.054). VFA/SFA (high vs. all the rest) results as a strong predictor of objective response (p = 0.02) and outcome (PFS, p = 0.001; OS, p = 0.02). At multivariate analysis for PFS, prognostic factors are VFA/SFA (p = 0.03) and a neutrophil–lymphocyte ratio >3. The same factors remain significant for OS (each p = 0.03) along with Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.008) and number of metastatic sites ≥2 (p < 0.001). In our cohort of aGC, VFA/SFA exhibit a robust impact on survival, with a higher sensitivity than sarcopenia.
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Affiliation(s)
- Silvia Catanese
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
| | - Giacomo Aringhieri
- Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy; (G.A.); (R.T.); (F.B.)
- Diagnostic and Interventional Radiology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.V.); (C.C.)
| | - Caterina Vivaldi
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
- Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy; (G.A.); (R.T.); (F.B.)
- Correspondence: ; Tel.: +39-050-992466
| | - Francesca Salani
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
| | - Saverio Vitali
- Diagnostic and Interventional Radiology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.V.); (C.C.)
| | - Irene Pecora
- Unit of Medical Oncology, Ospedale della Misericordia di Grosseto, Azienda Usl Sud Est, Via Senese 161, 58100 Grosseto, Italy;
| | - Valentina Massa
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
| | - Monica Lencioni
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
| | - Enrico Vasile
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
| | - Rachele Tintori
- Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy; (G.A.); (R.T.); (F.B.)
| | - Francesco Balducci
- Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy; (G.A.); (R.T.); (F.B.)
| | - Alfredo Falcone
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
- Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy; (G.A.); (R.T.); (F.B.)
| | - Carla Cappelli
- Diagnostic and Interventional Radiology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.V.); (C.C.)
| | - Lorenzo Fornaro
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy; (S.C.); (F.S.); (V.M.); (M.L.); (E.V.); (A.F.); (L.F.)
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Yan H, Chen Y, Yang Z, Li Z, Che X, Xiao J, Liu Y, Qu X. An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer. Front Immunol 2021; 11:621623. [PMID: 33613554 PMCID: PMC7890018 DOI: 10.3389/fimmu.2020.621623] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/21/2020] [Indexed: 12/20/2022] Open
Abstract
Increasing evidence has indicated that current tumor-node-metastasis (TNM) stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stages II and III gastric cancer (GC) patients after surgery. In order to improve the predictive ability of survival and adjuvant chemotherapy benefits of GC patients after surgery, this study aimed to establish an immune signature based on the composition of infiltrating immune cells. Twenty-eight types of immune cell fractions were evaluated based on the expression profiles of GC patients from the Gene Expression Omnibus (GEO) database using single-sample gene set enrichment analysis (ssGSEA). The immunoscore (IS) was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model. Through the LASSO model, an IS classifier consisting of eight immune cells was constructed. Significant difference was found between high-IS and low-IS groups in the training cohort in disease-free survival (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). Multivariate analysis showed that the IS classifier was an independent prognostic indicator. Moreover, a combination of IS and TNM stage exhibited better prognostic value than TNM stage alone. Further analysis demonstrated that low-IS patients who had more tumor-infiltrating lymphocytes had better response to adjuvant chemotherapy. More importantly, we found that patients with high-IS were more likely to benefit from a Xeloda plus cisplatin regimen after surgery. Finally, we established two nomograms to screen the stage II and III GC patients who benefitted from adjuvant chemotherapy after surgery. The combination of IS classifier and TNM stage could predict DFS and OS of GC patients. The IS model has been proven as a promising tool that can be used to identify the patients with stages II and III GC who may benefit from adjuvant chemotherapy.
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Affiliation(s)
- Hongfei Yan
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
| | - Yang Chen
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China
| | - Zichang Yang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
| | - Zhi Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
| | - Xiaofang Che
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
| | - Jiawen Xiao
- Department of Medical Oncology, Shenyang Fifth People Hospital, Shenyang, China
| | - Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
| | - Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, China
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12
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The Dichotomous Role of Bone Marrow Derived Cells in the Chemotherapy-Treated Tumor Microenvironment. J Clin Med 2020; 9:jcm9123912. [PMID: 33276524 PMCID: PMC7761629 DOI: 10.3390/jcm9123912] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/23/2020] [Accepted: 11/27/2020] [Indexed: 12/19/2022] Open
Abstract
Bone marrow derived cells (BMDCs) play a wide variety of pro- and anti-tumorigenic roles in the tumor microenvironment (TME) and in the metastatic process. In response to chemotherapy, the anti-tumorigenic function of BMDCs can be enhanced due to chemotherapy-induced immunogenic cell death. However, in recent years, a growing body of evidence suggests that chemotherapy or other anti-cancer drugs can also facilitate a pro-tumorigenic function in BMDCs. This includes elevated angiogenesis, tumor cell proliferation and pro-tumorigenic immune modulation, ultimately contributing to therapy resistance. Such effects do not only contribute to the re-growth of primary tumors but can also support metastasis. Thus, the delicate balance of BMDC activities in the TME is violated following tumor perturbation, further requiring a better understanding of the complex crosstalk between tumor cells and BMDCs. In this review, we discuss the different types of BMDCs that reside in the TME and their activities in tumors following chemotherapy, with a major focus on their pro-tumorigenic role. We also cover aspects of rationally designed combination treatments that target or manipulate specific BMDC types to improve therapy outcomes.
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Wen F, Huang J, Lu X, Huang W, Wang Y, Bai Y, Ruan S, Gu S, Chen X, Shu P. Identification and prognostic value of metabolism-related genes in gastric cancer. Aging (Albany NY) 2020; 12:17647-17661. [PMID: 32920549 PMCID: PMC7521523 DOI: 10.18632/aging.103838] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/14/2020] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is one of the most commonly occurring cancers, and metabolism-related genes (MRGs) are associated with its development. Transcriptome data and the relevant clinical data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and we identified 194 MRGs differentially expressed between GC and adjacent nontumor tissues. Through univariate Cox and lasso regression analyses we identified 13 potential prognostic differentially expressed MRGs (PDEMRGs). These PDEMRGs (CKMT2, ME1, GSTA2, ASAH1, GGT5, RDH12, NNMT, POLR1A, ACYP1, GLA, OPLAH, DCK, and POLD3) were used to build a Cox regression risk model to predict the prognosis of GC patients. Further univariate and multivariate Cox regression analyses showed that this model could serve as an independent prognostic parameter. Gene Set Enrichment Analysis showed significant enrichment pathways that could potentially contribute to pathogenesis. This model also revealed the probability of genetic alterations of PDEMRGs. We have thus identified a valuable metabolic model for predicting the prognosis of GC patients. The PDEMRGs in this model reflect the dysregulated metabolic microenvironment of GC and provide useful noninvasive biomarkers.
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Affiliation(s)
- Fang Wen
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Jiani Huang
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,College of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xiaona Lu
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wenjie Huang
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yulan Wang
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Hematology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yingfeng Bai
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,College of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Shuai Ruan
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Suping Gu
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Xiaoxue Chen
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Peng Shu
- Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China,Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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14
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Clinicopathological and prognostic significance of platelet-lymphocyte ratio (PLR) in gastric cancer: an updated meta-analysis. World J Surg Oncol 2020; 18:191. [PMID: 32731872 PMCID: PMC7391520 DOI: 10.1186/s12957-020-01952-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 07/07/2020] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Pre-treatment PLR (platelet-lymphocyte ratio) was reported to be associated with the prognosis in gastric cancer (GC), but the results remain inconclusive. This meta-analysis aimed to investigate the prognostic potential of the pre-treatment PLR in gastric cancer. METHODS We performed a systematic literature search in PubMed, Embase, and the Cochrane Library to identify eligible publications. The hazard ratio (HR)/odds ratio (OR) and its 95% confidence (CI) of survival outcomes and clinicopathological parameters were calculated. RESULTS A total of 49 studies (51 cohorts), collecting data from 28,929 GC patients, were included in the final analysis. The pooled results demonstrated that the elevated pre-treatment PLR was significantly associated with poor overall survival (OS) (HR 1.37, 95% CI 1.26-1.49, p < 0.001; I2 = 79.90%, Ph < 0.001) and disease-free survival (DFS) (HR 1.52, 95% CI 1.22-1.90, p < 0.001, I2 = 88.6%, Ph < 0.001). Furthermore, the patients with the elevated PLR had a higher risk of lymph node metastasis (OR = 1.17, 95% CI 1.02-1.33, p = 0.023), serosal invasion (T3+T4) (OR = 1.34, 95% CI 1.10-1.64, p = 0.003), and increased advanced stage (III+IV) (OR = 1.20, 95% CI 1.06-1.37, p = 0.004). CONCLUSIONS An elevated pre-treatment PLR was a prognostic factor for poor OS and DFS and associated with poor clinicopathological parameters in GC patients.
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Zhao G, Liu N, Wang S, Guo J, Song X, Qi Y, Qiu W, Lv J. Prognostic significance of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in patients with metastatic gastric cancer. Medicine (Baltimore) 2020; 99:e19405. [PMID: 32150090 PMCID: PMC7478543 DOI: 10.1097/md.0000000000019405] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Advanced gastric cancer has a poor prognosis because of advanced gastric cancer is prone to metastasis. It is urgent for us to find an indicator to predict the prognosis of gastric cancer in a timely fashion. Research has revealed that inflammation has an important role in predicting survival in some cancers. The purpose of this study was to evaluate the significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of metastatic gastric cancer (GC).This was a retrospective review of 110 patients were at presentation diagnosed with stage IV metastatic GC and all patients received palliative chemotherapy between January 2012 and January 2016 at the Affiliated Hospital of Qingdao University. Pretreatment NLR and PLR, as well as clinicopathological characteristics were collected. Patients were divided into high and low groups according to the cutoff values for NLR and PLR. The Kaplan-Meier method was applied to estimate the overall survival (OS) and the Cox proportional hazards model to evaluate the related risk factors for OS. All tests were 2-tailed and a P < .05 was considered to indicate a statistically significant difference.One hundred ten patients were enrolled. Eighty-four patients were men, 24 patients were women, 61 patients were ≥65 years of age, and 49 patients were <65 years of age. The Eastern Cooperative Oncology Group (ECOG) score of most patients (n = 107) ranged from 0 to 1. Ten patients were human epidermal growth factor receptor 2 (HER2)-positive. Seventy-one patients presented with an elevated carcinoembryonic antigen (CEA) level and 49 patients had an elevated Carcinoembryonic 199 (CA-199) level. Fifty-two patients received first-line chemotherapy only. Nineteen patients received third-line or greater chemotherapy. One hundred patients chose dual drug chemotherapy. The median duration of follow-up was 11.6 months. Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value for NLR and PLR was 2.48 and 143.39. Patients with high NLR and high PLR had poor overall survival compared with those who had low NLR and low PLR (P < .001 and P = .013, respectively). In univariate analysis, old age (P = .013), liver metastasis (P = .001), >1 metastatic sites (P = .028), higher NLR (P = .000), and higher PLR (P = .014) were identified as poor prognostic factors associated with OS. Our multivariate analysis had indicated that high NLR (hazard ratio [HR]: 1.617, 95% CI: 1.032-2.525, P = .036) and peritoneal metastasis (HR: 1.547, 95% CI:1.009-2.454, P = .045) was independent prognostic factors for overall survival; however, the PLR was not shown to be an independent prognostic factor.Our study suggested that the pretreatment NLR can be used as significant prognosis biomarker in metastatic gastric cancer patients receiving palliative chemotherapy.
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Cao W, Yao X, Cen D, Zhi Y, Zhu N, Xu L. The prognostic role of platelet-to-lymphocyte ratio on overall survival in gastric cancer: a systematic review and meta-analysis. BMC Gastroenterol 2020; 20:16. [PMID: 31959103 PMCID: PMC6971934 DOI: 10.1186/s12876-020-1167-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 01/10/2020] [Indexed: 01/19/2023] Open
Abstract
Background This study aimed to summarize the previously published literature on the role of platelet-to-lymphocyte ratio (PLR) on overall survival (OS) in patients with gastric cancer. Methods We systematically searched PubMed, EmBase, and the Cochrane library to identify eligible studies to review. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity and subgroup analyses were performed, and publication bias was assessed. Results A total of 28 studies comprising 15,617 patients with gastric cancer were included in this meta-analysis. The pooled results indicated that elevated PLR was associated with poor OS (HR: 1.37; 95% CI: 1.24–1.51; P < 0.001). A significant publication bias was observed (Egger test, P = 0.036; Begg test, P = 0.017). After adjusting for publication bias using the trim and fill method, an adjusted pooled HR of 1.19 (95% CI: 1.08–1.33; P = 0.001) was observed. Subgroup analyses indicated an elevated PLR in retrospective studies. Studies conducted in Turkey, the UK, the USA, and Costa Rica; studies with a sample size of < 1000, with < 70% male patients, and with patients treated with chemotherapy; studies with PLR cutoff value of ≥200; and studies with lower quality as determined by the Newcastle-Ottawa Scale all showed greater harmful effects on OS than their corresponding subsets (P < 0.05). Conclusions An elevated PLR was associated with poor OS in patients with gastric cancer. These results might differ between studies due to differences in design, country of origin, sample size, sex proportion, treatment strategy, PLR cutoff value, and study quality.
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Affiliation(s)
- Weijuan Cao
- College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang Province, China
| | - Xiaomin Yao
- College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang Province, China
| | - Danwei Cen
- College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang Province, China
| | - Yajun Zhi
- College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang Province, China
| | - Ningwei Zhu
- College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang Province, China
| | - Liyong Xu
- Zhejiang Pharmaceutical College, Ningbo Higher Education Park, No 888, East Section of Yinxian Avenue, Ningbo, 315100, Zhejiang Province, China.
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Shao Y, Tao X, Lu R, Zhang H, Ge J, Xiao B, Ye G, Guo J. Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction. Pathol Oncol Res 2019; 26:1475-1482. [PMID: 31432324 DOI: 10.1007/s12253-019-00716-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 08/12/2019] [Indexed: 02/07/2023]
Abstract
Circular RNAs (circRNAs) are an endogenous RNAs with a covalently closed cyclic structure. They have emerged recently as key regulators in the development and progression of human cancers. However, the clinical values of most circRNAs in gastric cancer (GC) are unknown. Hsa_circ_0065149, one of the dysregulated circRNAs in gastric carcinogenesis detected by circRNA microarray, was chose as a targeted circRNA in this study. We firstly enlarged sample size and identified the level changes of hsa_circ_0065149 among four stages of gastric tumorigenesis from healthy gastric mucosa, gastritis, intestinal metaplasia to GC. Then, the potential relationship between hsa_circ_0065149 expression levels and GC patients' clinicopathological factors was investigated. Moreover, the clinical significance of hsa_circ_0065149 in plasma exosomes and gastric juice were explored. Receiver operating characteristic (ROC) curve and Kaplan-Meier survival curve were constructed to evaluate diagnostic and prognostic values. Finally, bioinformatics analysis was performed to excavate the potential functions of hsa_circ_0065149. Hsa_circ_0065149 expression was only significantly down-regulated in gastric cancer, not changed among healthy gastric mucosa and gastritis intestinal metaplasia. Low hsa_circ_0065149 expression levels in GC tissues were significantly associated with tumor diameter (P = 0.034) and perineural invasion (P = 0.037). GC patients with low hsa_circ_0065149 levels had a much longer overall survival than those in high group (P = 0.020). More important, hsa_circ_0065149 levels were significantly decreased in plasma exosomes of early GC patients. As a screening biomarker for early GC, hsa_circ_0065149 in plasma exosomes has higher sensitivity and specificity than traditional clinical biomarkers. Bioinformatics analysis suggest that the abnormal expression of hsa_circ_0065149 may play an important role during gastric carcinogenesis. Those results indicate that hsa_circ_0065149 in exosmoes is an indicator for early GC screening and prognosis prediction.
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Affiliation(s)
- Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Xueping Tao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China
| | - Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Haiqiang Zhang
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Jiaxin Ge
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China.
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.
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Lu R, Shao Y, Tao X, Ye G, Xiao B, Guo J. Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues. J Clin Lab Anal 2019; 33:e22984. [PMID: 31328820 PMCID: PMC6868420 DOI: 10.1002/jcla.22984] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 06/29/2019] [Accepted: 07/02/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are a special class of endogenous noncoding RNAs that have numerous biological functions in normal situation and diseases including cancers. However, the clinical significance of circRNAs in gastric cancer (GC) remains largely unknown. Here, we chose two representative circRNAs, hsa_circ_0067582 and hsa_circ_0005758, to investigate their clinical significance in GC patients. METHODS Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we explored the expression levels of hsa_circ_0067582 and hsa_circ_0005758 in tissues with different stages of gastric tumorigenesis. Then, the relationships between their expression levels and GC patients' clinicopathological factors were further investigated. Receiver operating characteristic (ROC) curves were established for evaluating diagnostic values of hsa_circ_0067582 and hsa_circ_0005758. RESULTS Compared with healthy control tissues, both hsa_circ_0067582 and hsa_circ_0005758 were significantly decreased in GC tissues. Besides, hsa_circ_0067582 expression was associated with GC patients' tissue CEA level (P <.001) and stages (P = .037); and hsa_circ_0005758 expression was relevant to tissue CEA level (P < .001) and perineural invasion (P = .048). The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.671. The cutoff value was set at 10.61, with which the sensitivity and specificity were 55.2% and 75.0%, respectively. Similar to hsa_circ_0005758, the AUC of hsa_circ_0005758 was 0.721. The cutoff value was set at 10.20, with which the sensitivity and specificity were 75.0% and 67.7%, respectively. CONCLUSION These results showed that both hsa_circ_0067582 and hsa_circ_0005758 may play an important role in gastric carcinogenesis; and they may be potential indicators for GC diagnosis.
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Affiliation(s)
- Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Xueping Tao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
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The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells. Cancers (Basel) 2019; 11:cancers11020240. [PMID: 30791448 PMCID: PMC6406993 DOI: 10.3390/cancers11020240] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 01/29/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023] Open
Abstract
Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet⁻cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.
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Ahadi A, Safavi MS. miR-335-5p has an important role in the progression of gastric cancer by down-regulation of CEACAM5. Meta Gene 2019. [DOI: 10.1016/j.mgene.2018.10.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
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Mo X, Wu Y, Chen L, Zhai M, Gao Z, Hu K, Guo J. Global expression profiling of metabolic pathway-related lncRNAs in human gastric cancer and the identification of RP11-555H23.1 as a new diagnostic biomarker. J Clin Lab Anal 2018; 33:e22692. [PMID: 30320481 DOI: 10.1002/jcla.22692] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Revised: 09/20/2018] [Accepted: 09/21/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Long noncoding RNAs (lncRNAs) have roles in regulating metabolism; however, the global expression profile of metabolic pathway-associated lncRNAs in gastric cancer is unknown. The purpose of our study was to examine metabolic pathway-related lncRNAs in gastric cancer and their possible diagnostic values. METHODS Differential expression patterns of metabolic pathway-related lncRNAs between gastric cancer and paired nontumor tissues were detected using metabolic pathway-associated lncRNA microarrays. The expression of RP11-555H23.1, one representative metabolic pathway-associated lncRNA, was validated using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The associations between RP11-55H23.1 expression and the clinicopathological features of gastric cancer patients were analyzed. A receiver operating characteristic (ROC) curve was further established. RESULTS A total of 114 differentially expressed metabolic pathway-associated lncRNAs (fold change >2, P < 0.05) between cancer and nontumor tissues were found (GEO No. GSE96856). Among them, TUG1, RP11-555H23.1, RP1-257I20.13, UGP2, GCSHP3, and XLOC_000889 lncRNAs were downregulated more than sixfold in gastric cancer tissues. In contrast, RP11-605F14.2, TBC1D3P5, BC130595, LINC00475, RP11-19P22.6, BC080653, XLOC_004923, AFAP1-AS1, EPB49, and RP11-296I10.3 lncRNAs were upregulated more than sixfold in gastric cancer tissues. We further demonstrated that RP11-555H23.1 expression was significantly correlated with TNM stage (P = 0.038). The area under the ROC curve (AUC) was 0.65, and the specificity and sensitivity were 62% and 81%, respectively. CONCLUSIONS Metabolic pathway-associated lncRNAs play an important role in the occurrence of gastric cancer, and metabolic pathway-associated lncRNAs, such as RP11-555H23.1, may represent novel biomarkers of gastric cancer.
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Affiliation(s)
- Xiaoyan Mo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Yuanyuan Wu
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Li Chen
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Ming Zhai
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Zhengdong Gao
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Kainan Hu
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
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Zhu X, Chen F, Shao Y, Xu D, Guo J. Long intergenic non-protein coding RNA 1006 used as a potential novel biomarker of gastric cancer. Cancer Biomark 2018; 21:73-80. [PMID: 29060927 DOI: 10.3233/cbm-170273] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Accumulating evidences have shown that long non-coding RNAs (lncRNAs), longer than 200 nucleotides in length, play a crucial role in cancer occurrence and development. However, the relationships between most lncRNAs and gastric carcinogenesis remain poorly understood. OBJECTIVE To explore the diagnostic value of one typical lncRNA, long intergenic non-protein coding RNA 1006 (LINC01006), in gastric cancer. METHODS First, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression levels of LINC01006 in various gastric tissues from gastric cancer patients, healthy controls, and gastric dysplasia. Next, the correlation between LINC01006 expression levels and clinicopathological features of patients with gastric cancer was assessed. Finally, the relative levels of LINC01006 in gastric cancer cell lines comparing to normal gastric epithelial cell line were analyzed. RESULTS LINC01006 levels in cancer tissues were significantly lower than those in adjacent normal tissues (P< 0.001) and healthy control tissues (P< 0.001). Its expression was associated with age (P= 0.013), tumor location (P= 0.022), tumor size (P= 0.030), and venous invasion (P= 0.018). Moreover, expression of LINC01006 was downregulated in two gastric cancer cell lines, MGC-803 (P< 0.05) and AGS (P< 0.001) compared to normal gastric epithelial cell line GES-1. CONCLUSIONS All the data implied that LINC01006 may be a novel biomarker for gastric cancer.
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Mo X, Li T, Xie Y, Zhu L, Xiao B, Liao Q, Guo J. Identification and functional annotation of metabolism-associated lncRNAs and their related protein-coding genes in gastric cancer. Mol Genet Genomic Med 2018; 6:728-738. [PMID: 29992774 PMCID: PMC6160698 DOI: 10.1002/mgg3.427] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Revised: 04/17/2018] [Accepted: 06/11/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Long noncoding RNAs (lncRNAs) play important roles in carcinogenesis. However, the roles of metabolism-associated lncRNAs in cancers are still unclear. METHODS A microarray of metabolism-associated lncRNAs was used to detect their expression patterns between gastric cancer and paired nontumorous tissues. Its results and gastric cancer differential gene expression data from public databases were used to screen the metabolic pathway-associated lncRNAs. A metabolic network with microRNAs (miRNAs), lncRNAs, and protein-coding genes was further constructed. Finally, the expression of TOPORS antisense RNA 1 (TOPORS-AS1), a screened highly expressed lncRNA and its associated protein-coding gene, NADH: ubiquinone oxidoreductase subunit B6 (NDUFB6), were verified by reverse transcription polymerase chain reaction. RESULTS A total of eight upregulated and one downregulated lncRNAs and 25 upregulated and 20 downregulated protein-coding genes were found to be involved in metabolism in gastric cancer. Within the lncRNAs-miRNAs-mRNAs metabolic network, 78 miRNA-target links, 546 positive coexpression relationships, and 191 protein-protein interactions were found. The expression of TOPORS-AS1 and its associated gene, NDUFB6 in gastric cancer tissues was significantly lower than that in adjacent nontumor tissues. Moreover, NDUFB6 expression was associated with the invasion and distal metastasis of gastric cancer. CONCLUSIONS The metabolism-associated lncRNAs play important roles in the occurrence of gastric cancer.
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Affiliation(s)
- Xiaoyan Mo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Tianwen Li
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Yi Xie
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Linwen Zhu
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Qi Liao
- Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
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Zhang Y, Zhou H, Sun H, Chen J, Huang D, Han X, Ren X, Lin S, Fan Q, Tian W, Zhao Y. Association of peripheral blood leukocyte KIBRA methylation with gastric cancer risk: a case-control study. Cancer Med 2018; 7:2682-2690. [PMID: 29659170 PMCID: PMC6010778 DOI: 10.1002/cam4.1474] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 03/08/2018] [Accepted: 03/11/2018] [Indexed: 12/23/2022] Open
Abstract
KIBRA was reported to be involved in various types of cancer and can be detected in blood. The purpose of this study was to investigate the relationship between the status of KIBRA methylation in peripheral blood leukocytes and gastric cancer (GC) risk. A case-control study was carried out to evaluate the association of blood cell-derived KIBRA methylation with the risk of GC using methylation-sensitive high-resolution melting analysis. A total of 393 cases and 393 controls were detected, respectively. Compared with the subjects in the KIBRA negative methylation (NM) group, positive methylation (PM) subjects exhibited a 1.52-fold (95% CI: 1.030-2.251, P = 0.035) increased risk for GC. Stratified analyses demonstrated that the significant association of KIBRA methylation with GC risk existed in the older group (≥ 60 years; ORa = 1.846, 95% CI: 1.037-3.287, P = 0.037) and Helicobacter pylori (H. pylori) positive subjects (ORa = 1.933, 95% CI: 1.103-3.386, P = 0.021). Statistically significant combination effects between the environmental factors and KIBRA methylation on the GC risk were observed except for storing food under refrigeration. KIBRA methylation derived from blood cells and combinations thereof with environmental factors may be associated with the risk of GC.
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Affiliation(s)
- Yan Zhang
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Haibo Zhou
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Hongxu Sun
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Jie Chen
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Di Huang
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Xu Han
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Xiyun Ren
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Shangqun Lin
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Qing Fan
- Xiangfang Center for Disease Control and PreventionHarbinHeilongjiang ProvinceChina
| | - Wenjing Tian
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
| | - Yashuang Zhao
- Department of EpidemiologyCollege of Public HealthHarbin Medical UniversityHarbinHeilongjiang ProvinceChina
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Ni C, Yang P, Guo J, Ye M. Role of DiGeorge syndrome critical region gene 9, a long noncoding RNA, in gastric cancer. Onco Targets Ther 2018; 11:2259-2267. [PMID: 29719408 PMCID: PMC5914736 DOI: 10.2147/ott.s162253] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Introduction Long non-coding RNAs (lncRNAs) regulate and influence cancer cell development and tumor formation. However, the role for lncRNAs in gastric cancer has not been fully established. In this study, DGCR9, a lncRNA, was significantly upregulated in gastric cancer cell lines. Methods The expression levels of DGCR9 in each patient between formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues and adjacent noncancer tissues (NAT) (n=102) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DGCR9 on cellular proliferation, migration, and glucose uptake was investigated in vitro, respectively. Results DGCR9 was shown to have increased expression in gastric cancer tissues and in gastric cancer cell lines. Further, DGCR9 was found to be associated with clinicopathological characteristics of patients with gastric cancer. In particular, DGCR9 was positively associated with lymph node invasion and tumor-node-metastasis (TNM) stage in gastric cancer patients. By in vitro functional analysis, knockdown of DGCR9 in gastric cancer cells suppressed cellular proliferation, migration, and glucose uptake. In contrast, overexpression of DGCR9 increased each of these cancer cell characteristics. Conclusions DGCR9 was upregulated in gastric cancer tissues and was shown to accelerate cellular proliferation, migration, and glucose metabolism, all of which would promote the formation and development of gastric cancer.
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Affiliation(s)
- Chao Ni
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, People's Republic of China
| | - Ping Yang
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, People's Republic of China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, People's Republic of China
| | - Meng Ye
- Department of Medical Oncology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, People's Republic of China
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Xie Y, Shao Y, Sun W, Ye G, Zhang X, Xiao B, Guo J. Downregulated expression of hsa_circ_0074362 in gastric cancer and its potential diagnostic values. Biomark Med 2017; 12:11-20. [PMID: 29240459 DOI: 10.2217/bmm-2017-0114] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM To explore the diagnostic value of hsa_circ_0074362 in the screening of gastric cancer. METHODS The expression levels of hsa_circ_0074362 in 127 gastric cancer tissues and paired adjacent normal tissues, 83 gastritis tissues and six gastric cancer cell lines were first detected by quantitative reverse transcription-polymerase chain reaction. Then, the relationship between its levels and clinicopathological factors of patients with gastric cancer was analyzed. Finally, a receiver operating characteristic curve was established. RESULTS Hsa_circ_0074362 levels were significantly downregulated in gastric cancer tissues, gastritis tissues and gastric cancer cell lines. Its levels were associated with lymphatic metastasis. CONCLUSION Hsa_circ_0074362 probably plays a role in the initiation of gastric cancer and may be a potential biomarker of gastric cancer.
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Affiliation(s)
- Yi Xie
- Department of Biochemistry & Molecular Biology, & Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, PR China
| | - Yongfu Shao
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, PR China
| | - Weiliang Sun
- Ningbo Yinzhou People's Hospital & the Affiliated Hospital, Medical School of Ningbo University, Ningbo 315040, PR China
| | - Guoliang Ye
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, PR China
| | - Xinjun Zhang
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, PR China
| | - Bingxiu Xiao
- Department of Biochemistry & Molecular Biology, & Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, PR China
| | - Junming Guo
- Department of Biochemistry & Molecular Biology, & Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, PR China
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Zhao Q, Chen S, Li T, Xiao B, Zhang X. Clinical values of circular RNA 0000181 in the screening of gastric cancer. J Clin Lab Anal 2017; 32:e22333. [PMID: 28940688 DOI: 10.1002/jcla.22333] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 09/01/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are recently found involved in cancer occurrence and development. However, their values in the diagnosis of gastric cancers are largely unknown. In this study, we analyzed the values of hsa_circ_0000181 in the diagnosis of gastric cancer. METHODS Using divergent primers, hsa_circ_0000181 expression levels in fresh gastric cancer tissues and paired adjacent non-tumorous tissues, and plasmas from patient with gastric cancer and health people were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between hsa_circ_0000181 levels and the clinicopathologic features of patients with gastric cancer was further analyzed. Finally, to evaluate the diagnostic value, receiver operating characteristic (ROC) curve was established. RESULTS Hsa_circ_0000181 levels in gastric cancer tissues and plasma from gastric cancer patients were significantly decreased than those in paired adjacent non-tumorous tissues (P < .001) and healthy people (P < .001), respectively. Furthermore, hsa_circ_0000181 expression in gastric cancer tissues was significantly correlated with tumor diameter (P = .027), lymphatic metastasis (P = .044), distal metastasis (P = .023), and carbohydrate antigen 19-9 (P = .031). Its decreased levels in patients' plasma were significantly associated with differentiation (P = .038) and carcinoembryonic antigen (P = .037). The areas under ROC curve were 0.756. The specificity of tissue hsa_circ_0000181 and sensitivity of plasma hsa_circ_0000181 were 85.2% and 99.0%, respectively. CONCLUSIONS Thanks to the high stability, tissue and plasma hsa_circ_0000181 may be a novel biomarker for the diagnosis of gastric cancer.
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Affiliation(s)
- Qianfu Zhao
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Shijun Chen
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Tianwen Li
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Xinjun Zhang
- Department of Gastroenterology, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China
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Huang L, Wei ZJ, Li TJ, Jiang YM, Xu AM. A prospective appraisal of preoperative body mass index in D2-resected patients with non-metastatic gastric carcinoma and Siewert type II/III adenocarcinoma of esophagogastric junction: results from a large-scale cohort. Oncotarget 2017; 8:68165-68179. [PMID: 28978106 PMCID: PMC5620246 DOI: 10.18632/oncotarget.19251] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 06/16/2017] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To prospectively investigate associations of presurgical body mass index (BMI) with clinicopathological factors and its prognostic significance in radically D2-resected patients with non-metastasized gastric cancer (GC) and Siewert type II/III adenocarcinoma of esophagogastric junction (AEG). METHODS A large prospective cohort consisting of radically-resected GC and AEG patients was analyzed. Follow-up was successful in 671 out of 700 patients, who were categorized into underweight (BMI<18.5), normal-weight (BMI=18.5-22.9), overweight (BMI=23-24.9), and obese (BMI≥25) groups according to Asian standards. BMI-associated factors were explored using multivariable logistic regression with adjustment. Cancer-specific survival analyses were conducted applying both univariable and multivariable Cox regression methods. RESULTS Pre-operation, higher hemoglobin levels and smaller anemia proportions were observed in larger BMI groups. Higher BMI tended to be associated with higher neutrophil-lymphocyte ratios (NLRs). Patients with higher BMI had smaller tumors and more often stage I tumors, but longer surgical time and postsurgical stay. In multivariable analyses, higher hemoglobin levels, upper tumor location, poorer differentiation, and higher NLR were significantly associated with higher BMI. Overall, survival analyses revealed no significant role of BMI. However, in further stratifications after adjustment, compared to patients with normal BMI, obese patients had better survival in women, but worse in those with AEG; underweight was associated with reduced mortality risk in tumors differentiated well to moderately; overweight patients had increased death hazard when having thrombocytopenia. CONCLUSION Overall, preoperative BMI had limited prognostic significance in operated GC patients. However, under specific conditions (e.g., female, AEG, good differentiation, and thrombocytopenia), BMI might indicate postoperative survival.
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Affiliation(s)
- Lei Huang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhi-Jian Wei
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Tuan-Jie Li
- Department of General Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China
| | - Yu-Ming Jiang
- Department of General Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China
| | - A-Man Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China
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Tian M, Chen R, Li T, Xiao B. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal 2017; 32. [PMID: 28618205 DOI: 10.1002/jcla.22281] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 05/22/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. METHODS The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. RESULTS Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. CONCLUSIONS All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer.
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Affiliation(s)
- Mengqian Tian
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China
| | - Ruoyu Chen
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China
| | - Tianwen Li
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China
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Wang J, Qu J, Li Z, Che X, Liu J, Teng Y, Jin B, Zhao M, Liu Y, Qu X. Pretreatment platelet-to-lymphocyte ratio is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer. J Clin Lab Anal 2017; 32. [PMID: 28238215 DOI: 10.1002/jcla.22185] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/26/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Several studies have shown that platelet-to-lymphocyte ratio (PLR) is a prognostic factor for various cancers. However, there is no study about the role of PLR in predicting response to first-line chemotherapy of metastatic gastric cancer. Therefore, this study aimed to establish whether PLR is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer. METHODS We enrolled 273 patients diagnosed with metastatic gastric cancer. The best cut-off value of PLR to predict chemotherapeutic response was chosen by receiver operating characteristic (ROC) curve analysis. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis. RESULTS Based on the cut-off value of PLR, patients were divided into a low PLR group and high PLR group. In logistic regression analysis, the low PLR group had a significantly higher disease control rate than the high PLR group had (91.3 vs 76.1%, P=.002), and PLR was an independent risk factor for response to first-line chemotherapy (odds ratio [OR]: 3.256; 95% confidence interval [CI]: 1.521-6.969; P=.002). The low PLR group had significantly longer overall survival (OS) than the high PLR group had (13.4 vs 9.2 months; P=.020). Multivariate survival analysis showed that PLR was significantly associated with OS [hazard ratio (HR): 1.002; 95% CI: 1.000-1.003; P=.020]. CONCLUSIONS Pre-treatment PLR is associated with the response rate to first-line chemotherapy and survival outcomes in patients with metastatic gastric cancer.
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Affiliation(s)
- Jin Wang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Jinglei Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Zhi Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Xiaofang Che
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Jing Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Yuee Teng
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Bo Jin
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Mingfang Zhao
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
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