Combined identification of ARID1A, CSMD1, and SENP3 as effective prognostic biomarkers for hepatocellular carcinoma.
Combined identification of ARID1A, CSMD1, and SENP3 as effective prognostic biomarkers for hepatocellular carcinoma.
复制标题
联合鉴定 ARID1A、CSMD1 和 SENP3 作为肝细胞癌的有效预后生物标志物
DOI：
10.18632/aging.202586
复制
发表时间：
2021-02-07
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Zhao Y;Yang B;Chen D;Zhou X;Wang M;Jiang J;Wei L;Chen Z
背景：本研究旨在了解原发性肝细胞癌（HCC）的基因图谱，并探究其诊断和预后生物标志物。
方法：对36例感染乙型肝炎病毒（HBV）的中国HCC样本队列进行全外显子测序（WES）。确定与预后相关的变异，并在癌症基因组图谱（TCGA）数据库以及基因表达综合数据库（GEO）中的GSE65372数据集中进一步验证。收集180例感染HBV的中国HCC样本作为验证队列，通过免疫组化分析评估候选基因。采用受试者工作特征（ROC）曲线分析评估候选基因的预后预测能力。最后，通过5 - 乙炔基 - 2' - 脱氧尿苷（EdU）实验和Transwell侵袭实验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存在显著关联。利用GEO和TCGA数据库对数据进行了验证，并在验证队列中评估了AT丰富交互结构域1A（ARID1A）、CUB和Sushi多结构域蛋白1（CSMD1）以及类泛素特异性蛋白酶3（SENP3）的表达。此外，在验证队列人群中，ARID1A、CSMD1和SENP3是HCC患者有效的预后生物标志物。
结论：在HCC患者中检测到分子异质性，且ARID1A、CSMD1和SENP3被确定为有效的HCC预后生物标志物。CSMD1通过抑制细胞侵袭来预防HCC。
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.