联合鉴定、、和作为肝细胞癌的有效预后生物标志物。
Combined identification of , , and as effective prognostic biomarkers for hepatocellular carcinoma.
机构信息
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China.
出版信息
Aging (Albany NY). 2021 Feb 7;13(3):4696-4712. doi: 10.18632/aging.202586.
BACKGROUND
The current study aimed to understand the genetic landscape and investigate the diagnostic and prognostic biomarkers of primary hepatocellular carcinoma (HCC).
METHODS
A cohort of 36 Chinese HCC samples with hepatitis B virus (HBV) infection was examined by whole-exome sequencing (WES). Prognosis-related alterations were identified and further verified in the TCGA database and GSE65372 profiles in the GEO database. A Chinese replication cohort of 180 HCC samples with HBV infection was collected to evaluate the candidate genes by immunohistochemical analysis. A receiver operating characteristic (ROC) curve analysis evaluated the prognostic power of candidate genes. Finally, EdU and transwell invasion assay were performed to detect the function of candidate genes.
RESULTS
A total of 11 novel genes showed a significant association with HCC in the discovery cohort. The data were verified using the GEO and TCGA databases, and the expression of ARID1A, CSMD1, and SENP was evaluated in the replication cohort. Furthermore, ARID1A, CSMD1, and SENP3 are effective prognostic biomarkers for HCC patients in the replication population.
CONCLUSIONS
Molecular heterogeneity was detected in HCC patients, and ARID1A, CSMD1, and SENP3 were identified as effective HCC prognosis biomarkers. CSMD1 prevents HCC by suppressing cell invasion.
背景
本研究旨在了解原发性肝细胞癌（HCC）的遗传特征，并探索其诊断和预后生物标志物。
方法
对 36 例乙型肝炎病毒（HBV）感染的中国 HCC 样本进行全外显子组测序（WES）。在 TCGA 数据库和 GEO 数据库的 GSE65372 谱中鉴定并进一步验证与预后相关的改变。收集了 180 例乙型肝炎病毒感染的中国 HCC 样本复制队列，通过免疫组织化学分析来评估候选基因。利用受试者工作特征（ROC）曲线分析来评估候选基因的预后能力。最后，通过 EdU 和 Transwell 侵袭实验来检测候选基因的功能。
结果
在发现队列中，共有 11 个新基因与 HCC 具有显著相关性。利用 GEO 和 TCGA 数据库对这些数据进行了验证，并在复制队列中评估了 ARID1A、CSMD1 和 SENP 的表达。此外，ARID1A、CSMD1 和 SENP3 是复制人群中 HCC 患者的有效预后生物标志物。
结论
在 HCC 患者中检测到分子异质性，并且鉴定出 ARID1A、CSMD1 和 SENP3 是有效的 HCC 预后生物标志物。CSMD1 通过抑制细胞侵袭来预防 HCC。
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