Clinical Significance and Potential Mechanisms of ATP Binding Cassette Subfamily C Genes in Hepatocellular Carcinoma

Overview

Journal Front Genet

Date 2022 Mar 28

PMID 35342392

Authors

Xin Zhou

Jia-Mi Huang

Tian-Man Li

Jun-Qi Liu

Zhong-Liu Wei

Chen-Lu Lan

Guang-Zhi Zhu

Xi-Wen Liao

Xin-Ping Ye

Tao Peng

Affiliations

Soon will be listed here.

Abstract

The purpose of this investigation was to assess the diagnostic and prognostic significance of genes in hepatocellular carcinoma (HCC). The Student t-test was used to compare the expression level of 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 , , , and were significantly upregulated in tumor tissues, while and were downregulated in HCC tissues. Receiver operating characteristic analysis revealed that might be a potential diagnostic biomarker in HCC. , , , and were significantly related to the prognosis of HCC in the TCGA database. The prognostic significance of , , , and 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 was associated with tumor differentiation, nod-like receptor signal pathway, and so forth. It also revealed that might play a role in HCC by regulating epithelial-mesenchymal transition, cytidine analog pathway, met pathway, and so forth. might be associated with the fatty acid metabolism and KRT19 in HCC. 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, , , , and might be prognostic biomarkers in HCC. The prognostic models constructed with , , , and had satisfactory efficacy.

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