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Wang JH, Li XS, Tang HS, Fang RY, Song JJ, Feng YL, Guan TP, Ruan Q, Wang J, Cui SZ. Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:4163-4172. [PMID: 36050540 DOI: 10.1007/s00432-022-04323-4] [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: 07/27/2022] [Accepted: 08/22/2022] [Indexed: 01/27/2023]
Abstract
PURPOSE Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit. METHODS Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC-) was evaluated. RESULTS The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC- patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC- , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC- ones, may be not due to the activation of HIF-1α pathway. CONCLUSION The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients' outcomes and responses to adjuvant TACE therapy.
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Affiliation(s)
- Jia-Hong Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Xiao-Shan Li
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Hong-Sheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Run-Ya Fang
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Jing-Jing Song
- Department of Pathology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Yan-Lin Feng
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Tian-Pei Guan
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Qiang Ruan
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China
| | - Jin Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China.
| | - Shu-Zhong Cui
- Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China.
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Chen WY, Li C, Liu ZP, Kong QY, Sun LY, Zeng YY, Liang YJ, Zhou YH, Chen TH, Chen ZX, Wang MD, Yao LQ, Lau WY, Pawlik TM, Shen F, Ji JS, Yang T. Novel online calculator to predict reduced risk of early recurrence from adjuvant transarterial chemoembolisation for patients with hepatocellular carcinoma. EGASTROENTEROLOGY 2023; 1:e100008. [PMID: 39944245 PMCID: PMC11770458 DOI: 10.1136/egastro-2023-100008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 02/20/2023] [Indexed: 02/20/2025]
Abstract
BACKGROUND The role of adjuvant transarterial chemoembolisation (TACE) to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma (HCC). Personalised predictive tool to select which patients may benefit from adjuvant TACE is lacking. This study aimed to develop and validate an online calculator for estimating the reduced risk of early recurrence from adjuvant TACE for patients with HCC. METHODS From a multi-institutional database, 2590 eligible patients undergoing curative-intent hepatectomy for HCC were enrolled, and randomly assigned to the training and validation cohorts. Independent predictors of early recurrence within 1 year of surgery were identified in the training cohort, and subsequently used to construct a model and corresponding prediction calculator. The predictive performance of the model was validated using concordance indexes (C-indexes) and calibration curves, and compared with conventional HCC staging systems. The reduced risk of early recurrence when receiving adjuvant TACE was used to estimate the expected benefit from adjuvant TACE. RESULTS The prediction model was developed by integrating eight factors that were independently associated with risk of early recurrence: alpha-fetoprotein level, maximum tumour size, tumour number, macrovascular and microvascular invasion, satellite nodules, resection margin and adjuvant TACE. The model demonstrated good calibration and discrimination in the training and validation cohorts (C-indexes: 0.799 and 0.778, respectively), and performed better among the whole cohort than four conventional HCC staging systems (C-indexes: 0.797 vs 0.562-0.673, all p<0.001). An online calculator was built to estimate the reduced risk of early recurrence from adjuvant TACE for patients with resected HCC. CONCLUSIONS The proposed calculator can be adopted to assist decision-making for clinicians and patients to determine which patients with resected HCC can significantly benefit from adjuvant TACE.
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Affiliation(s)
- Wei-Yue Chen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research, Department of Interventional Radiology, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Zhi-Peng Liu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qing-Yu Kong
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Li-Yang Sun
- Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Pu’er, Yunnan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People’s Hospital, Ziyang, Sichuan, China
| | - Zi-Xiang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Jian-Song Ji
- The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research, Department of Interventional Radiology, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
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Liang J, Bai Y, Ha FS, Luo Y, Deng HT, Gao YT. Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:1-18. [PMID: 36684055 PMCID: PMC9850755 DOI: 10.4251/wjgo.v15.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/06/2022] [Accepted: 12/28/2022] [Indexed: 01/10/2023] Open
Abstract
Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.
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Affiliation(s)
- Jing Liang
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Yi Bai
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Fu-Shuang Ha
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying Luo
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Hui-Ting Deng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying-Tang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
- Tianjin Institute of Hepatobiliary Disease, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
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Wang C, Ding ZW, Zheng CG, Wang S, Li ZH, Zhang ZM, Pan J, Wang J, Yang C. COCH predicts survival and adjuvant TACE response in patients with HCC. Oncol Lett 2021; 21:275. [PMID: 33732351 PMCID: PMC7905559 DOI: 10.3892/ol.2021.12536] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 01/06/2021] [Indexed: 12/12/2022] Open
Abstract
The aim of the present study was to measure the expression of Cochlin (COCH) and analyze its association with survival, recurrence and the benefits from adjuvant transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Patients with high COCH expression levels had a poorer prognosis in terms of overall and disease-free survival rate compared with those with low COCH expression levels. Further analysis revealed that patients with low COCH expression who received TACE experienced markedly lower early recurrence rates compared with those who did not receive TACE. However, patients with high COCH expression with and without adjuvant TACE after resection experienced no difference in disease recurrence rates. The expression of COCH was found to be associated with hepatitis B virus infection, portal vein tumor thrombosis and Barcelona Clinic Liver Cancer stage in HCC. Therefore, the findings of the present study indicated that clinical detection of COCH expression may help estimate the prognosis of patients with HCC, as well as determine whether to administer TACE after surgery to prevent recurrence.
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Affiliation(s)
- Chen Wang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China.,Department of Pediatric Surgery, Hangzhou Children's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Zhi-Wen Ding
- Department of Hepatobiliary Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 201805, P.R. China
| | - Cheng-Gang Zheng
- Department of Hyperbaric Medicine, Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China
| | - Siyuan Wang
- Suzhou Institute of Drug Control, Suzhou, Jiangsu 215031, P.R. China
| | - Zhi-Heng Li
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
| | - Zi-Mu Zhang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
| | - Jian Pan
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
| | - Jian Wang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
| | - Chun Yang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
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Beneficial effects of Cripto-1 for transarterial chemoembolization in hepatocellular carcinoma. Aging (Albany NY) 2020; 11:2998-3011. [PMID: 31136302 PMCID: PMC6555445 DOI: 10.18632/aging.101951] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 04/30/2019] [Indexed: 01/27/2023]
Abstract
Cripto-1 may act as an independent predictor for prognosis in hepatocellular carcinoma (HCC). However, the function of Cripto-1 in HCC cells and its response to postoperative transarterial chemoembolization (TACE) in HCC patients remains unclearly. Up-regulated Cripto-1 expression boosted the ability of cell proliferation, migration and invasion in HCC cells in vitro. While opposite results were observed in HCC cells with down-regulated Cripto-1 expression. Cripto-1 expression was correlated with epithelial-mesenchymal transition (EMT) relevant biomarkers. Furthermore, in high Cripto-1 expression patients, those with adjuvant TACE had favorable TTR and OS times. On contrary, adjuvant TACE may promote tumor recurrence but had no influence on OS time in patients with low Cripto-1 expression. In different subgroups of vascular invasion, larger tumor size or liver cirrhosis, patients with adjuvant TACE had longer TTR and OS times than those without TACE in patients with high Cripto-1 expression, while they could not obtain benefits from adjuvant TACE in patients with low-expressed Cripto-1 expression. In conclusion, Cripto-1 may be a potential prognostic factor in predicting outcome of HCC patients with TACE therapy, and combined with Cripto-1 and tumor features may be helpful to stratify patients with respect to prognosis and response to adjuvant TACE.
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Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, Gu WM, Wang H, Chen TH, Zeng YY, Li C, Wu MC, Shen F, Yang T. Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study From China. JAMA Surg 2019; 154:209-217. [PMID: 30422241 DOI: 10.1001/jamasurg.2018.4334] [Citation(s) in RCA: 364] [Impact Index Per Article: 60.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. Objective To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. Design, Setting, and Participants This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. Interventions Liver resection for HCC. Main Outcomes and Measures Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. Results Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. Conclusions and Relevance Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.
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Affiliation(s)
- Xin-Fei Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.,Department of Clinical Medicine, Second Military Medical University, Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.,Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, the Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Yang H, Wang J, Li Z, Yang Y, Yang L, Zhang Y, Shi Y, Cao Y, Zhou J, Wang Z, Chen Q. Risk Factors and Outcomes of Early Relapse After Curative Resection of Intrahepatic Cholangiocarcinoma. Front Oncol 2019; 9:854. [PMID: 31555597 PMCID: PMC6737003 DOI: 10.3389/fonc.2019.00854] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 08/19/2019] [Indexed: 12/24/2022] Open
Abstract
Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382-2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061-2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095-2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120-2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367-2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331-2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409-2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.
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Affiliation(s)
- Hua Yang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Jie Wang
- ENT Institute and Otorhinolaryngology Department, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Zehuan Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Liuxiao Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Yong Zhang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Yinghong Shi
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Ya Cao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Cancer Research Institute, Central South University, Ministry of Education, Changsha, China
| | - Jian Zhou
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,State key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Zheng Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Qing Chen
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
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Wang JH, Zhong XP, Zhang YF, Wu XL, Li SH, Jian PE, Ling YH, Shi M, Chen MS, Wei W, Guo RP. Cezanne predicts progression and adjuvant TACE response in hepatocellular carcinoma. Cell Death Dis 2017; 8:e3043. [PMID: 28880268 PMCID: PMC5636974 DOI: 10.1038/cddis.2017.428] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 07/18/2017] [Accepted: 07/20/2017] [Indexed: 02/07/2023]
Abstract
We have previously reported that Cezanne could be a prognostic biomarker for survival in hepatocellular carcinoma (HCC) patients. However, the role of Cezanne genes in HCC cells and its response to postoperative adjuvant transcatheter arterial chemoembolization (TACE) in HCC patients remains unknown. In this study, Cezanne expression was detected in human HCC using real-time PCR, western blot and immunohistochemistry. The function of Cezanne in HCC cells was determined by Transwell invasion assays and nude mice metastasis assay. The response of Cezanne in patients who received adjuvant TACE after hepatectomy was evaluated. Functional study demonstrated that interference of Cezanne expression promoted the migration and invasion of HCC cells in vitro and boosted metastasized HCC formation in mice. Upregulation of Cezanne diminished the adhesion and migration of hepatoma cells. Further study indicated that Cezanne might inhibit invasion of HCC cells by inducing epithelial-mesenchymal transition (EMT). In addition, patients with low Cezanne expression had significant improvement in prognosis after receiving adjuvant TACE. In contrast, patients with high Cezanne expression had a poorer response to adjuvant TACE. Moreover, Cezanne status was associated with response to adjuvant TACE in patients subgroup stratified by vascular invasion, tumor size and tumor number. In conclusion, Cezanne may be a novel antioncogene that has a pivotal role in the invasion of HCC and contribute to the selection of patients who may benefit from adjuvant TACE to prevent recurrence.
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Affiliation(s)
- Jia-Hong Wang
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Abdominal Surgery, Affiliated Cancer Hospital &Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiao-Ping Zhong
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong-Fa Zhang
- Department of Liver Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiao-Liang Wu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Shao-Hua Li
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Pei-En Jian
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yi-Hong Ling
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ming Shi
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Min-Shan Chen
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wei Wei
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Rong-Ping Guo
- Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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9
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Zhang J, Jiang TY, Jiang BG, Yang C, Tan YX, Yang N, Pan YF, Ding ZW, Yang GZ, Wu MC, Dong LW, Wang HY. RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma. Oncotarget 2016; 6:3432-42. [PMID: 25605019 PMCID: PMC4413664 DOI: 10.18632/oncotarget.3092] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Accepted: 12/25/2014] [Indexed: 01/26/2023] Open
Abstract
Adjuvant transcatheter arterial chemoembolization (TACE) protects against hepatocellular carcinoma (HCC) and is associated with reduced disease recurrence and improved outcome after surgery. However, deterioration of liver function after TACE negatively impacts the patient prognosis and limits it use as an option to prolong survival. We analyzed two independent cohorts that included a total of 510 patients with HCC who had undergone tumor resection. Immunohistochemistry assay was used to measure RPB5-mediating protein (RMP) expression and assessed their association with recurrence rate and response to therapy with adjuvant TACE. In patients with HCC, the expression of RMP in tumor is associated with age, gender, tumor size, portal venous invasion, TNM stages, BCLC stages and overall survival. Among patients with high RMP expression, adjuvant TACE after resection was associated with early recurrence. Even in the patients with small tumor size (no more than 5 cm) or no venous invasion, RMP status is associated with response to adjuvant TACE. RMP status in tumors may be a useful marker in estimating prognosis in patients with HCC and in assisting in the selection of patients who are likely to benefit from adjuvant TACE to prevent relapse.
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Affiliation(s)
- Jian Zhang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China.,Current address: Department of Cardiac Surgery, General Hospital of Shenyang Military Area Command, Shenyang, P. R. China
| | - Tian-Yi Jiang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Bei-Ge Jiang
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Chun Yang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Ye-Xiong Tan
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Ning Yang
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Yu-Fei Pan
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Zhi-Wen Ding
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Guang-Zhen Yang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China
| | - Meng-Chao Wu
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China
| | - Li-Wei Dong
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China
| | - Hong-Yang Wang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.,National Center for Liver Cancer, Shanghai, P.R. China.,State Key Laboratory of Oncogenes and related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, P.R. China
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