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Identification of portal vein tumor thrombus with an independent clonal origin in hepatocellular carcinoma via multi-omics data analysis

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Cancer Biology & Medicine 2019年第1期16卷 147-156页

作者： Shupeng Liu Zaixin Zhou Yin Jia Jie Xue Zhiyong Liu Kai cheng shuqun cheng Shanrong Liu Clinical Research Center Changhai Hospital Second Military Medical University Department of Laboratory Diagnostics Changhai Hospital Second Military Medical University Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery Hospital Second Military Medical University

Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the *** analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual *** gene expression analysis was applied to investigate the gene expression profiles of PVTTs and ***: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene ***: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in *** results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.

关键词： Hepatocellular carcinoma portal vein tumor thrombus clonal origin copy number variation bioinformatics

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Typing of biliary tumor thrombus influences the prognoses of patients with hepatocellular carcinoma

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Cancer Biology & Medicine 2021年第3期18卷 808-815页

作者： Juxian Sun Jiayi Wu Chang Liu Jie Shi Yonggang Wei Jianyin Zhou Zhibo Zhang Wan Yee Lau Maolin Yan shuqun cheng Department of Hepatic SurgeryⅥ The Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200433China Shengli Clinical Medical College Fujian Medical UniversityFuzhou 350001China Department of Hepatobiliary Surgery Fujian Provincial HospitalFuzhou 350001China Department of Hepatobiliary Surgery West China HospitalSichuan UniversityChengdu 610041China Department of Hepatobiliary Surgery Zhongshan HospitalXiamen UniversityXiamen 361004China Department of Hepatobiliary Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350002China Faculty of Medicine The Chinese University of Hong KongHong Kong 999077China

Objective:To establish a new classification of biliary tumor thrombus(BTT).Methods:Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging *** and multivariate analyses were used to determine factors affecting the overall survival(OS)to form the basis of our new classification for ***:All 6 international staging systems showed overlapping survival *** followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of *** on these data,a new BTT classification was defined as:TypeⅠ:intrahepatic BTT;and TypeⅡ:extrahepatic BTT involving a common bile duct or common hepatic ***Ⅰwas further subdivided into type Ia:BTT involving a second-order intrahepatic duct or above,and type Ib:BTT involving a first-order intrahepatic ***Ⅱwas further subdivided into typeⅡa and typeⅡb using a cut-off total bilirubin(TB)>300μmol/*** numbers(percentages)of patients with typesⅠandⅡBTT were 69(34.2%)and 133(65.8%),*** median OS of typeⅠpatients was significantly higher than that of typeⅡpatients(37.5 months vs.23.2 months;P=0.002).Using subgroup analyses,OS outcomes were significantly different between the subgroups of typeⅡb and type IIa,although there was no significant difference between the type Ia and type Ib subgroups(P=0.07).Conclusions:A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.

关键词： Hepatocellular carcinoma biliary tumor thrombus staging system surgery prognosis

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Modulation of Behavior and Glutamate Receptor mRNA Expression in Rats after Sub-chronic Administration of Benzo(a)pyrene

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Biomedical and Environmental Sciences 2011年第4期24卷 408-414页

作者： TANG Qian XIA YinYin cheng shuqun TU BaiJie Department of Occupational and Environmental Medicine College of Public Health Chongqing MedicalUniversity Chongqing 400016 Sichuan China

Objective The present study aimed to test whether exposure to benzo（a）pyrene [B（a）P] affects spatial learning and short-term memory by modulating the expression of the Gria1 and Grin2a glutamate receptor subunit genes in the *** Thirty-six 21-24-day-old,male rats were randomly assigned into high-,medium-,and low-dose toxin exposure groups （6.25,2.5,and 1 mg/kg,respectively） and a control group,each containing nine *** behavioral performance of adult rats exposed to sub-chronic administration of B（a）P was monitored by learning and memory tests （Morris water maze）.Real-time PCR assays were used to quantify Gria1 and Grin2a gene expression in the *** At medium and high doses,B（a）P impaired spatial learning *** crossing-platform-location frequency and the time spent swimming in the platform area,which both relate to short-term memory,were significantly decreased in B（a）P-treated rats compared with *** level of Gria1 mRNA increased 2.6-5.9-fold,and the level of Grin2a mRNA increased 10-14.5-fold,with a greater fold increase associated with higher doses of B（a）*** We demonstrated that sub-chronic administration of B（a）P inhibits spatial learning and short-term memory,and increases Gria1 and Grin2a expression in the *** suggests a relationship of B（a）P exposure levels with Gria1 and Grin2a expression and impairment of short-term and spatial memory.

关键词： Benzo(a)pyrene Gria1 Grin2a

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Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5096-5105页

作者： Juxian Sun Feifei Mao Chang Liu Fan Zhang Dafeng Jiang Weixing Guo Lei Huo Liping Zhou Wan Yee Lau Jie Shi shuqun cheng Department of Hepatic Surgery VI Third Affliated Hospital of Naval Medical UniversityShanghaiChina Tongji University Cancer Center Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghaiChina Department of General Surgery Fujian Cancer HospitalFujan Medical UniversityFuzhouChina Department of Oncology Zhejiang Sian International HospitalJiaxingChina Department of Radiology Third Affliated Hospital of Naval Medical UniversityShanghaiChina Faculty of Medicine The Chinese University of Hong KongPrince of Wales HospitalShatinNew TerritoriesHong Kong SARChina

The majority of hepatocellular carcinoma(HCC)cases are diagnosed at an advanced ***,there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis(EHM).Systemic chemotherapy,such as FOLFOX4(infusions of fluorouracil,leucovorin,and oxaliplatin),has been reported for treating advanced HCC with EHM,but its effectiveness is very poor.

关键词： FOLFOX4 metastasis chemotherapy

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肝细胞癌伴门静脉癌栓的降期治疗

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临床肝胆病杂志 2020年第2期36卷 263-266页

作者：程树群卫旭彪海军军医大学附属东方肝胆外科医院肝外六科

肝细胞癌伴门静脉癌栓发生率高,病情进展快,现有治疗方法有限且效果不佳。虽然国外指南推荐索拉非尼为唯一治疗手段,但临床研究显示部分患者,尤其是伴癌栓侵犯至门静脉一级或二级分支的患者(程氏分型Ⅰ/Ⅱ型),通过手术切除可以取得比其... 详细信息

肝细胞癌伴门静脉癌栓发生率高,病情进展快,现有治疗方法有限且效果不佳。虽然国外指南推荐索拉非尼为唯一治疗手段,但临床研究显示部分患者,尤其是伴癌栓侵犯至门静脉一级或二级分支的患者(程氏分型Ⅰ/Ⅱ型),通过手术切除可以取得比其他非手术疗法更好的效果。然而临床实践中相当一部分患者由于病灶范围较广无法根治性切除,或者由于癌栓侵犯到门静脉主干(程氏Ⅲ型),术后癌栓残留可能性高,需要通过降期切除的方法改善预后。研究发现通过新辅助三维适形放疗、经肝动脉钇-90微球放射性栓塞、肝动脉灌注化疗等姑息性治疗方法,部分患者(5.7%~26.5%)可出现门静脉癌栓消退乃至消失、肿瘤体积缩小、卫星灶消失等现象,从而使病灶降期,提高手术切除率并延长患者生存时间。多学科综合治疗对于进一步提高肝细胞癌伴门静脉癌栓患者的降期切除率至关重要。

关键词：癌,肝细胞门静脉癌栓治疗学

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脂肪酸转运体与肿瘤侵袭转移

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中华实验外科杂志 2019年第9期36卷 1708-1710页

作者：张帆程树群苏州大学第三附属医院肝胆外科常州213000 海军军医大学附属东方肝胆外科医院肝外六科上海200438

CD36又称脂肪酸转运体(FAT),是一种单链跨膜糖蛋白,属于B族清道夫受体,可识别多种配体,并参与多种正常和病理过程.近年来的研究结果表明CD36可能通过调节血管生成、上皮-间充质转化、肿瘤微泡外溢、脂代谢重构等环节在肿瘤侵袭转移中发... 详细信息

CD36又称脂肪酸转运体(FAT),是一种单链跨膜糖蛋白,属于B族清道夫受体,可识别多种配体,并参与多种正常和病理过程.近年来的研究结果表明CD36可能通过调节血管生成、上皮-间充质转化、肿瘤微泡外溢、脂代谢重构等环节在肿瘤侵袭转移中发挥重要作用.本文拟对CD36的结构与正常功能以及CD36在肿瘤侵袭转移中的研究作一综述.

关键词：脂肪酸转运体肿瘤侵袭转移

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Chinese expert consensus on clinical application of molecularly targeted drugs for hepatocellular carcinoma (2022 edition)

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中华医学杂志(英文版) 2024年第21期137卷 2630页

作者： Sun Juxian Li Qiu Bai Xueli Cai Jianqiang Chen Yajin Chen Minshan Dai Chaoliu Fang Chihua Jia Weidong Li Xiangcheng Wen Tianfu Xia Jinglin Ying Mingang Zhang Zhiwei Zhang Xuewen Zeng Zhaochong cheng shuqun Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery Hospital Naval Medical University Shanghai China Department of Medical Oncology Cancer Center West China Hospital Sichuan University Chengdu Sichuan China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China Department of Hepatobiliary Surgery Cancer Hospital Chinese Academy of Medical Sciences Beijing China Department of Hepatobiliopancreatic Surgery Sun Yat-Sen Memorial Hospital Sun Yat-Sen University Guangzhou Guangdong China Department of Hepatobiliary Surgery Sun Yat-sen University Cancer Center Guangzhou Guangdong China Department of Hepatobiliary and Spleenary Surgery The Affiliated Shengjing Hospital China Medical University Shenyang Liaoning China Department of Hepatobiliary Surgery Zhujiang Hospital First Military Medical University Guangzhou Guangdong China Department of General Surgery Anhui Key Laboratory of Hepatopancreatobiliary Surgery Anhui Provincial Hospital The First Affiliated Hospital of USTC University of Science and Technology of China Hefei Anhui China Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Key Laboratory of Living Donor Liver Transplantation Nanjing Jiangsu China Department of Liver Surgery West China Hospital of Sichuan University Chengdu Sichuan China The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China Liver Cancer Institute & Zhongshan Hospital Fudan University Shanghai China Department of Gastrointestinal Oncological Surgery Fujian Provincial Cancer Hospital Fujian Medical University Teaching Hospital Fuzhou Fujian China Department of Surgery Hepatic Surgery Center Institute of HBP Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Department of Hepatobiliary and Pancreas Surgery The Second Hospital of Jilin University Changc

[3] Many targeted drugs have been developed for different treatment purposes and for different patient populations, and the way in which these therapies are selected to achieve a maximum benefit has been left up to individual clinicians due to the absence of authoritative guidelines.After progression is observed by imaging during treatment with first-line targeted drugs, a timely comprehensive evaluation should be performed to determine the appropriate second-line treatment (IIb, B).Many clinical studies have demonstrated that molecularly targeted drugs are effective treatments for advanced HCC, as they have good objective response rate (ORRs) and obvious survival benefits.Funding This work is supported by grants from the State Key Project of the National Natural Science Foundation of China (No. 81730097), the Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center (Joint Project of Emerging Frontier Technology) (No.

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Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum

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Chinese Journal of Cancer Research 2014年第5期26卷 588-595页

作者： Yufu Tang Hongming Yu Long Zhang Kang Wang Weixing Guo Jie Shi Shupeng Liu Mengchao Wu Hongyang Wang shuqun cheng Eastern Hepatobiliary Surgery Hospital Second Military Medical University Department of Hepatobiliary Surgery General Hospital of Shenyang Military Area Command Changhai Hospital Second Military Medical University International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute Second Military Medical University

Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）. Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metasta

关键词： Hepatocellular carcinoma(HCC) portal vein portal vein tumor thrombus(PVTT) metastasis

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A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study

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Chinese Medical Journal 2022年第19期135卷 2338-2343页

作者： Juxian Sun Chang Liu Jie Shi Nanya Wang Dafeng Jiang Feifei Mao Jingwen Gu Liping Zhou Li Shen Wan Yee Lau shuqun cheng Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Integrative Oncology Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Outpatient Department Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200433China Department of Oncology First Hospital of Jlin UniversityChangchunJlin 1300China Department of Oncology Zhejiang Sian International Hospital JiaxingZhejang 314000China Tongji University Cancer Center Shanghai Tenth People's HospitaSchool of MedicineTongji UniversitShanghai 200040China Faculty of Medicine The Chinese University of Hong KongPrince of Wales HospitalShatinNew TerritoriesHong Kong SAR 999077China.

Background:Chemotherapy is a common treatment for advanced hepatocellular carcinoma,but the effect is not *** study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid(ATRA)to infusional fluorouracil,leucovorin,and oxaliplatin(FOLFOX4)for advanced hepatocellular carcinoma(HCC).Methods:We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital,First Hospital of Jilin University,and Zhejiang Sian International Hospital and retrospectively compared for overall *** Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age,sex,and disease ***:From July 2013 to July 2018,111 patients with HCC were included in this *** median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group(P<0.001).The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group(3.6 monthsvs.1.8 months,P<0.001).Hazard ratios for overall survival and disease progression were 0.465(95%confidence interval:0.298–0.726;P=0.001)and 0.474(0.314–0.717;P<0.001)after adjusting for potential confounders,***:ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.

关键词： Hepatocellular carcinoma ATRA plus FOLFOX4 Overall survival All-trans-retinoic acid Fluorouracil Leucovorin Oxaliplatin

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提高进展期（巴塞罗那分期C期）肝细胞癌疗效的有效途径

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中华外科杂志 2015年第5期53卷 324-327页

作者：程树群卫旭彪吴孟超第二军医大学附属东方肝胆外科医院上海200433

相对于早中期肝癌,进展期肝癌（国际巴塞罗那分期C期）指首诊时即发现有门静脉癌栓形成或伴有淋巴结转移和肝外转移等表现的肝癌.进展期肝癌的治疗手段有限,预后极差.欧美指南对这一期肝癌的治疗手段仅限为口服甲苯磺酸索拉非尼,但临床... 详细信息

相对于早中期肝癌,进展期肝癌（国际巴塞罗那分期C期）指首诊时即发现有门静脉癌栓形成或伴有淋巴结转移和肝外转移等表现的肝癌.进展期肝癌的治疗手段有限,预后极差.欧美指南对这一期肝癌的治疗手段仅限为口服甲苯磺酸索拉非尼,但临床实际疗效不理想.国内的治疗手段则包括外科切除、介入化疗、放疗及传统中医药等.最新研究结果显示,以门静脉癌栓的“程氏分型”为基础,采用术前放疗降期后切除癌栓、术后早期使用甲苯磺酸索拉非尼及重视术后抗病毒治疗等手段能够有效地提高肝癌合并门静脉癌栓患者的疗效.对于合并淋巴结转移或肝外转移的肝癌,使用改良的Folfox4系统化疗方案有望改善预后.多学科协作团队模式能够更加科学合理地诊治合并门静脉癌栓或淋巴结转移及肝外转移的肝癌患者,是未来发展的趋势,也是提高疗效的有效途径.

关键词：肝肿瘤预后术前放疗抗病毒治疗分子靶向治疗

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