Table2_Clinical Significance and Potential Mechanisms of ATP Binding Cassette Subfamily C Genes in Hepatocellular Carcinoma.XLSX

The purpose of this investigation was to assess the diagnostic and prognostic significance of ATP binding cassette subfamily C (ABCC) genes in hepatocellular carcinoma (HCC). The Student t-test was used to compare the expression level of ABCCs between HCC and paraneoplastic tissues. Receiver operating characteristic curve (ROC) analysis was applied for diagnostic efficiency assessment. The Kaplan–Meier method and Cox proportional hazards model were respectively applied for survival analysis. Genes with prognostic significance were subsequently used to construct prognostic models. From the perspective of genome-wide enrichment analysis, the mechanisms of prognosis-related ABCC genes were attempted to be elaborated by gene set enrichment analysis (GSEA). It was observed in the TCGA database that ABCC1, ABCC4, ABCC5, and ABCC10 were significantly upregulated in tumor tissues, while ABCC6 and ABCC7 were downregulated in HCC tissues. Receiver operating characteristic analysis revealed that ABCC7 might be a potential diagnostic biomarker in HCC. ABCC1, ABCC4, ABCC5, and ABCC6 were significantly related to the prognosis of HCC in the TCGA database. The prognostic significance of ABCC1, ABCC4, ABCC5, and ABCC6 was also observed in the Guangxi cohort. In the Guangxi cohort, both polymerase chain reaction and IHC (immunohistochemical) assays demonstrated higher expression of ABCC1, ABCC4, and ABCC5 in HCC compared to liver tissues, while the opposite was true for ABCC6. GSEA analysis indicated that ABCC1 was associated with tumor differentiation, nod-like receptor signal pathway, and so forth. It also revealed that ABCC4 might play a role in HCC by regulating epithelial-mesenchymal transition, cytidine analog pathway, met pathway, and so forth. ABCC5 might be associated with the fatty acid metabolism and KRT19 in HCC. ABCC6 might impact the cell cycle in HCC by regulating E2F1 and myc. The relationship between ABCC genes and immune infiltration was explored, and ABCC1,4,5 were found to be positively associated with infiltration of multiple immune cells, while ABCC6 was found to be the opposite. In conclusion, ABCC1, ABCC4, ABCC5, and ABCC6 might be prognostic biomarkers in HCC. The prognostic models constructed with ABCC1, ABCC4, ABCC5, and ABCC6 had satisfactory efficacy.

本研究旨在探讨ATP结合盒亚家族C（ATP binding cassette subfamily C，ABCC）基因在肝细胞癌（hepatocellular carcinoma，HCC）中的诊断与预后价值。本研究采用Student t检验比较肝细胞癌与癌旁组织中ABCC基因的表达水平；应用受试者工作特征曲线（Receiver operating characteristic curve，ROC）分析评估其诊断效能；分别采用Kaplan–Meier法与Cox比例风险模型进行生存分析。随后选取具有预后意义的基因构建预后模型。从全基因组富集分析视角，通过基因集富集分析（Gene Set Enrichment Analysis，GSEA）阐明预后相关ABCC基因的潜在作用机制。在TCGA数据库中，我们观察到ABCC1、ABCC4、ABCC5及ABCC10在肿瘤组织中显著高表达，而ABCC6与ABCC7在肝细胞癌组织中呈低表达。受试者工作特征分析显示，ABCC7或可作为肝细胞癌潜在的诊断生物标志物。在TCGA数据库中，ABCC1、ABCC4、ABCC5及ABCC6与肝细胞癌预后显著相关；该预后关联在广西队列中同样得到验证。在广西队列中，聚合酶链反应与免疫组化（immunohistochemical，IHC）检测均显示，ABCC1、ABCC4及ABCC5在肝细胞癌组织中的表达高于正常肝组织，而ABCC6则呈相反趋势。基因集富集分析结果表明，ABCC1与肿瘤分化、Nod样受体信号通路等相关；ABCC4或通过调控上皮间质转化、胞苷类似物通路、Met通路等参与肝细胞癌的发生发展；ABCC5或与肝细胞癌的脂肪酸代谢及KRT19相关；ABCC6可能通过调控E2F1与myc影响肝细胞癌的细胞周期。本研究还探讨了ABCC基因与免疫浸润的关联，发现ABCC1、4、5的表达与多种免疫细胞浸润呈正相关，而ABCC6则与之相反。综上，ABCC1、ABCC4、ABCC5及ABCC6或可作为肝细胞癌的预后生物标志物；基于上述基因构建的预后模型具有良好的预测效能。