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

查看全文 作　　者：Shupeng [1]Liu;Zaixin [2]Zhou;Yin [2]Jia;Jie [3]Xue;Zhiyong [2]Liu;Kai [1]Cheng;Shuqun [3]Cheng;Shanrong [2]Liu 高影响力作者 机构地区：[1]Clinical Research Center, Changhai Hospital, Second Military Medical University;[2]Department of Laboratory Diagnostics, Changhai Hospital, Second Military Medical University;[3]Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University高影响力机构 出　　处：《Cancer Biology & Medicine》索引2019年第16卷第1期,共10页高影响力期刊 基　　金：supported by grants of China National Funds for Distinguished Young Scientists (Grant No. 81425019);National Natural Science Foundation of China (Grant No. 81672899);the State Key Program of National Natural Science Foundation of China (Grant No. 81730076);Shanghai Science and Technology Committee Program (Grant No. 18XD1405300);Specially-Appointed Professor Fund of Shanghai (Grant No. GZ2015009) 摘　　要：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 analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: 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 signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The 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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