| 摘要: |
| 基于加权基因共表达网络分析(Weighted gene co-expression network analysis,WGCNA)和基因富集分析(Gene set enrichment analysis,GSEA)筛选肝细胞癌的潜在生物标志物和治疗靶点。利用GEO数据库中的GEO2R在线工具对肝细胞癌和癌旁组织的基因进行差异分析,并对差异表达基因进行GO功能和KEGG通路富集分析。利用WGCNA与STRING两种算法提取关键核心(Hub)基因。然后通过GEPIA数据库中的转录数据对Hub基因的表达进行验证。Kaplan-Meier法分析各Hub基因的预后价值。此外,还使用 TIMER数据库和Spearman分析方法计算Hub基因表达与免疫细胞浸润的相关性。利用实时荧光定量RT-PCR检测6例肝细胞癌和癌旁组织中Hub基因的相对表达量。GSEA分析结果包括系统性红斑狼疮和补体和凝血级联过程。GO功能分析主要涉及淋巴细胞免疫、补体激活反应、体液免疫应答等。KEGG主要集中于补体激活、Th17细胞分化,Th1和Th2细胞分化等信号通路。研究发现C8a,C6与Mbl2基因的转录水平明显低于健康对照组,基因的表达与肝细胞癌患者的临床预后有关,同时与免疫细胞的激活也存在相关性。PCR结果显示,肝细胞癌中C8a,C6和Mbl2基因的mRNA表达水平显著低于正常组织(P<0.05)。核心基因C6,C8a和Mbl2有望成为潜在的肝细胞癌诊断生物标志物,参与补体通路,与影响肿瘤细胞免疫浸润相关,可作为临床诊断和治疗潜在治疗靶点。 |
| 关键词: 肝细胞癌 生物标志物 miRNA 免疫浸润 |
| DOI：10.12113/202308007 |
| 分类号:R735.7 |
| 文献标识码:A |
| 基金项目:内蒙古医科大学科技百万项目(No.YKD2020KJBW(LH)037). |
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| Potential biomarkers of hepatocellular arcinoma based on weighted gene co-expression network analysis |
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ZHANG Zhanying1 , JIANG Chunlin2 ,WU Aining3
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(1.Department of Clinical Laboratory, Bayannaoer Hospital, Bayannaoer 015002, Inner Mongolia, China;2.Department of Clinical Laboratory, Xingan League Peoples Hospital of Ulanhot, Ulanhot 137499, Inner Mongolia, China;3. Obstetrical department, The Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010030, China)
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| Abstract: |
| The study employs Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) to identify potential biomarkers and therapeutic targets for hepatocellular carcinoma.GEO2R in the GEO database is utilized for the analysis of the differentially expressed genes in hepatocellular carcinoma and paracancer tissue, and the enrichment of DEGs in Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways is assessed. Hub genes are extracted by WGCNA and STRING. Transcriptional data of Hub genes are verified by gene expression profiling interactive analysis (GEPIA). The prognostic significance of each Hub gene is assessed by the Kaplan-Meier method. Furthermore, the correlation between Hub gene expression and immune cell infiltration is determined through the utilization of the TIMER database and Spearman analysis. The relative expression of Hub genes in six cases of hepatocellular carcinoma and adjacent tissues is measured using real-time fluorescence quantitative RT-PCR.The results of the GSEA analysis reveal the involvement of systemic lupus erythematosus and complement and coagulation cascade processes. The functional analysis of the GO primarily encompass lymphocyte immunity, complement activation response, humoral immune response, and other related aspects. KEGG primarily concentrats on complement activation, Th17, Th1 and Th2 cell differentiation, and various signaling pathways. In this study, we observe a significant decrease in the transcription levels of C8a, C6,and Mbl2genes in comparison to healthy controls. Furthermore, we find a correlation between the expression of Hub genes and the clinical prognosis of patients with hepatocellular carcinoma, as well as their association with immune cell activation. The findings from the polymerase chain reaction (PCR) analysis indicat a significant decrease in the mRNA expression levels of the C8a, C6,and Mbl2genes in hepatocellular carcinoma compared to normal tissues (P<0.05). These core genes, namely C6, C8a,and Mbl2,hold promise as potential diagnostic biomarkers for hepatocellular carcinoma. Additionally, they are involved in the complement pathway and have implications in tumor cell immune invasion, making them potential targets for clinical diagnosis and therapeutic interventions. |
| Key words: Hepatocellular carcinoma Biomarkers miRNA Immune infiltration |
