Construction of a competing endogenous RNA network related to the prognosis of cholangiocarcinoma and comprehensive analysis of the immunological correlation

Abstract

Background: Cholangiocarcinoma (CCA) is a malignant tumor of the digestive system, with occult onset in the early stage, a high degree of malignancy in the late stage, and poor prognosis. At present, the pathogenesis of CCA is not clear, and there is a lack of effective immunotherapy. The purpose of this study was to identify the potential regulatory mechanism of CCA and analyze the possibility of its related immunotherapy. Methods: The circular RNAs (circRNAs) expression profile data of CCA was downloaded from the Gene Expression Omnibus (GEO) database; the miRNA and mRNA expression profile data of CCA were downloaded from The Cancer Genome Atlas (TCGA) database. Prognostic factors were screened by univariate Cox regression analysis, and the competing endogenous RNA (ceRNA) network was constructed via survival analysis. Multivariate Cox analysis was used to screen the independent prognostic factors and construct a prognostic correlation subnetwork. Analyzing the tumor microenvironment of CCA and survival analysis were performed according to the score of the microenvironment, and the distribution of tumor infiltrating immune cells (TICs) in CCA was calculated using the CIBERSORT algorithm. We explored the expression pattern of the target genes in pan-cancer, and the correlation between the key genes in the ceRNA subnetwork, TICs and immune checkpoints was analyzed using an online database. Finally, the expression levels of target genes were validated based on the Human Protein Atlas (HPA) databases. Results: We screened four circRNAs, 10 miRNAs, and 17 mRNAs with significant differences, and constructed the ceRNA network. Independent prognostic factors were screened by multivariate Cox regression analysis, and a subnetwork containing five nodes (hsa_circ_0002073→hsa-mir-4524a-3p→SLC16A3/SLC35E4/DDX4) was constructed. Further analysis showed that SLC16A3 was not only an independent posterior factor of CCA, but was also closely correlated with immune cells, immune checkpoints, and immunotherapy, and had a certain regulatory effect on the tumor microenvironment. Conclusions: Our study identified a novel prognostic marker of CCA, SLC16A3, and revealed the regulatory role of SLC16A3 in the tumor microenvironment, which is expected to provide new insights for the early diagnosis, prognosis, and targeted therapy of CCA.