Long Yao, Wang Wei, Liu Shouping, Wang Xiang, Tao Yongguang
Cancer Research Institute; School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Cell Oncol (Dordr). 2024 Dec;47(6):2297-2316. doi: 10.1007/s13402-024-01019-4. Epub 2024 Dec 24.
Our study aims to develop and validate a novel molecular marker for the prognosis and diagnosis of hepatocellular carcinoma (HCC) MATERIALS & METHODS: We retrospectively analyzed mRNA expression profile and clinicopathological data of HCC patients fetched from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and The International Cancer Genome Consortium (ICGC) datasets. Univariate Cox regression analysis was performed to collect differentially expressed mRNA (DEmRNAs) from HCC and non-tumor tissues, and YEATS2, a prognostic marker, was identified by further analysis. ROC curve, survival analysis and multivariate Cox regression analysis as well as nomograms were used to evaluate the prognosis of this gene. Finally, the biological function of this gene was preliminarily discussed by using single gene Gene Set Enrichment Analysis (GSEA), and the YEATS2 overexpression and knockdown hepatoma cell line was used to verify the results in vitro and in vivo.
Based on the clinical information of HCC in TCGA, GEO and ICGC databases, the gene YEATS2 with significant differences from HCC was identified. There was a statistical difference in the survival prognosis between the two databases and the ROC curve showed that the survival of HCC in both TCGA, GSE14520 and ICGC groups had a satisfactory predictive effect. Univariate and multivariate Cox regression analysis showed that YEATS2 was an independent prognostic factor for HCC, and Nomograms, which combined this prognostic feature with significant clinical features, provided an important reference for the clinical prognostic diagnosis of HCC. Next, we constructed overexpression and knockdown YEATS2 cell line in Hep3B and LM3 cells, and further proved that overexpression YEATS2 promote the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays, and knockdown YEATS2 inhibited the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays. Finally, the biological function of YEATS2 was preliminarily explored through GSEA analysis of a single gene, and it was found that it was significantly correlated with cell cycle and DNA repair, which provided us with ideas for further analysis. Furthermore, the knockdown of YEATS2 promoted radiation-induced DNA damage, enhanced radiosensitivity, and ultimately inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo.
Our study identified a promising prognostic marker for hepatocellular carcinoma that is useful for clinical decision-making and individualized treatment.
本研究旨在开发并验证一种用于肝细胞癌（HCC）预后和诊断的新型分子标志物。
我们回顾性分析了从癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和国际癌症基因组联盟（ICGC）数据集中获取的HCC患者的mRNA表达谱和临床病理数据。进行单变量Cox回归分析以从HCC和非肿瘤组织中收集差异表达的mRNA（DEmRNAs），并通过进一步分析鉴定出一种预后标志物YEATS2。使用ROC曲线、生存分析、多变量Cox回归分析以及列线图来评估该基因的预后。最后，通过单基因基因集富集分析（GSEA）初步探讨该基因的生物学功能，并使用YEATS2过表达和敲低的肝癌细胞系在体外和体内验证结果。
基于TCGA、GEO和ICGC数据库中HCC的临床信息，鉴定出与HCC有显著差异的基因YEATS2。两个数据库之间的生存预后存在统计学差异，ROC曲线显示TCGA、GSE14520和ICGC组中HCC的生存具有令人满意的预测效果。单变量和多变量Cox回归分析表明，YEATS2是HCC的独立预后因素，将该预后特征与重要临床特征相结合的列线图为HCC的临床预后诊断提供了重要参考。接下来，我们在Hep3B和LM3细胞中构建了YEATS2过表达和敲低细胞系，并通过CCK8、集落形成实验和Transwell实验进一步证明，过表达YEATS2可促进HCC细胞的增殖和迁移，敲低YEATS2则通过CCK8、集落形成实验和Transwell实验抑制HCC细胞的增殖和迁移。最后，通过单基因GSEA分析初步探索了YEATS2的生物学功能，发现其与细胞周期和DNA修复显著相关，这为我们进一步分析提供了思路。此外，敲低YEATS2可促进辐射诱导的DNA损伤，增强放射敏感性，并最终在体外和体内抑制肝癌细胞的增殖。
我们的研究鉴定出一种有前景的肝细胞癌预后标志物，对临床决策和个体化治疗有用。
