Zhang Qifan, Xiao Zhen, Sun Shibo, Wang Kai, Qian Jianping, Cui Zhonglin, Tao Tao, Zhou Jie
Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People's Republic of China.
College of Life Sciences, Shanghai Normal University, Shanghai, 200234, People's Republic of China.
Cancer Manag Res. 2021 Mar 11;13:2307-2317. doi: 10.2147/CMAR.S291811. eCollection 2021.
Liver hepatocellular carcinoma (HCC) is the third most common cause of death by cancer and has a high mortality world-widely. Approximately 75-85% of primary liver cancers are caused by HCC. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient's outcome.
In this research, we aim to identify novel prognostic biomarkers in hepatocellular carcinoma.
Integrated proteomics and bioinformatics analysis were performed to investigate the expression landscape of prognostic biomarkers in 24 paired HCC patients.
As a result, eight key genes related to prognosis, including ACADS, HSD17B13, PON3, AMDHD1, CYP2C8, CYP4A11, SLC27A5, CYP2E1, were identified by comparing the weighted gene co-expression network analysis (WGCNA), proteomic differentially expressed genes (DEGs), proteomic turquoise module, The Cancer Genome Atlas (TCGA) cohort DEGs of HCC. Furthermore, we trained and validated eight pivotal genes integrating these independent clinical variables into a nomogram with superior accuracy in predicting progression events, and their lower expression was associated with a higher stage/risk score. The Gene Set Enrichment Analysis (GSEA) further revealed that these key genes showed enrichment in the HCC regulatory pathway.
All in all, we found that these eight genes might be the novel potential prognostic biomarkers for HCC and also provide promising insights into the pathogenesis of HCC at the molecular level.
肝细胞癌(HCC)是癌症死亡的第三大常见原因,在全球范围内具有很高的死亡率。大约75-85%的原发性肝癌由HCC引起。发现具有预后意义的新基因将有助于改善HCC患者的预后。
在本研究中,我们旨在识别肝细胞癌中新的预后生物标志物。
进行综合蛋白质组学和生物信息学分析,以研究24对HCC患者中预后生物标志物的表达情况。
通过比较加权基因共表达网络分析(WGCNA)、蛋白质组学差异表达基因(DEGs)、蛋白质组学绿松石模块、肝癌的癌症基因组图谱(TCGA)队列DEGs,确定了八个与预后相关的关键基因,包括ACADS、HSD17B13、PON3、AMDHD1、CYP2C8、CYP4A11、SLC27A5、CYP2E1。此外,我们将这些独立的临床变量整合到一个列线图中,对八个关键基因进行训练和验证,该列线图在预测进展事件方面具有更高的准确性,并且它们的低表达与更高的分期/风险评分相关。基因集富集分析(GSEA)进一步表明,这些关键基因在HCC调控途径中表现出富集。
总之,我们发现这八个基因可能是HCC新的潜在预后生物标志物,也为HCC发病机制的分子水平研究提供了有前景的见解。