Shu Jinyong, Luo Pan, Zhang Guifeng, Gao Yi
General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Oncology, Yueyang Central Hospital, Yueyang, China.
J Gastrointest Oncol. 2023 Apr 29;14(2):636-649. doi: 10.21037/jgo-23-247. Epub 2023 Apr 27.
Hepatocellular carcinoma (HCC) has a high incidence, and current treatments are ineffective. We aimed to explore potential diagnostic and prognostic biomarkers for HCC by conducting bioinformatics analysis on genomic and proteomic data.
Genome and proteome data were downloaded from The Cancer Genome Atlas (TCGA) and ProteomeXchange databases, respectively. Differentially expressed genes was determined using limma package. Functional enrichment analysis was conducted by Database for Annotation, Visualization, and Integrated Discovery (DAVID). Protein-protein analysis was established by STRING dataset. Using Cytoscope for network visualization and CytoHubba for hub gene identification. The gene mRNA and protein levels were validated using GEPIA and HPA, as well as RT-qPCR and Western blot.
A total of 127 up-regulated and 80 down-regulated common DEGPs were identified between the genomic and proteomic data, Mining 10 key genes/proteins(ACLY, ACACB, EPRS, CAD, HSPA4, ACACA, MTHFD1, DMGDH, ALDH2, and GLDC) through protein interaction networks. in addition, Glutamyl-prolyl-tRNA synthetase (EPRS) was highlighted as an HCC biomarker that is negatively correlated with survival. Differential EPRS expression analysis in HCC and paracancerous tissues showed that EPRS expression was elevated in HCC. RT-qPCR and Western blot analysis results showed that EPRS expression was upregulated in HCC cells.
Our results suggest that EPRS is a potential therapeutic target for inhibiting HCC tumorigenesis and progression.
肝细胞癌（HCC）发病率高，目前的治疗方法效果不佳。我们旨在通过对基因组和蛋白质组数据进行生物信息学分析，探索HCC潜在的诊断和预后生物标志物。
分别从癌症基因组图谱（TCGA）和蛋白质组交换数据库下载基因组和蛋白质组数据。使用limma软件包确定差异表达基因。通过注释、可视化和综合发现数据库（DAVID）进行功能富集分析。利用STRING数据集进行蛋白质-蛋白质分析。使用Cytoscope进行网络可视化，使用CytoHubba进行枢纽基因鉴定。通过GEPIA和HPA以及RT-qPCR和蛋白质免疫印迹法验证基因的mRNA和蛋白质水平。
在基因组和蛋白质组数据之间共鉴定出127个上调和80个下调的常见差异表达基因对（DEGPs），通过蛋白质相互作用网络挖掘出10个关键基因/蛋白质（ACLY、ACACB、EPRS、CAD、HSPA4、ACACA、MTHFD1、DMGDH、ALDH2和GLDC）。此外，谷氨酰胺-脯氨酰-tRNA合成酶（EPRS）被确定为与生存呈负相关的HCC生物标志物。HCC组织和癌旁组织中EPRS差异表达分析表明，HCC中EPRS表达升高。RT-qPCR和蛋白质免疫印迹分析结果显示，HCC细胞中EPRS表达上调。
我们的结果表明，EPRS是抑制HCC肿瘤发生和进展的潜在治疗靶点。
