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Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma

Xiaoli Chen, Jianing Chen, Yan Feng, Wei Guan

Department of Pathology, The First People’s Hospital of Nantong, Nantong, Jiangsu, China (mainland)

Med Sci Monit 2020; 26:e925016

DOI: 10.12659/MSM.925016

Available online: 2020-07-24

Published: 2020-09-19

BACKGROUND: SLC4A4 is differentially expressed in a variety of tumors, but its significance in colon adenocarcinoma has not been determined.
MATERIAL AND METHODS: Transcriptomes of two cohorts, GSE41258 and GSE32323, contained in The Cancer Genome Atlas (TCGA) were analysed to determine differences in SLC4A4 expression between tumor and normal tissue and their correlations with overall survival. The relationships between SLC4A4 expression and clinical characteristics were determined by COX regression analysis and logistic regression analysis, and correlations of SLC4A4 levels with tumor infiltrating immune cells (TIICs) and genes with high mutation frequency were evaluated by Pearson correlation analysis. Molecular functions and signaling pathways that might be affected by changes in SLC4A4 expression were determined by gene set enrichment analysis (GSEA). The overall distribution of TIICs was determined by two web servers: tumor immune estimation resource (TIMER) and CIBERSORT.
RESULTS: SLC4A4 expression was lower in colon adenocarcinoma than in normal colon tissue, suggesting that SLC4A4 was associated with poor prognosis. Reduced SLC4A4 expression was also associated with lymph node invasion and distant metastasis and was moderately correlated with increased expression of MUC4 and SMAD4, two genes with high mutation frequency in colon adenocarcinoma. GSEA indicated that changes in SLC4A4 expression affects several biological processes, including mismatch repair, base excision repair, and DNA replication. Eight TIICs in the tumor microenvironment differed significantly in groups with low and high expression of SLC4A4.
CONCLUSIONS: SLC4A4 may be a novel biomarker predicting prognosis in patients with colon adenocarcinoma. TIICs differed significantly in samples with higher and lower expression of SLC4A4.

Keywords: Adenocarcinoma, Prognosis, Sodium-Bicarbonate Symporters