Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Abstract

Abstract The expression level of SLC35A3 is related to the prognosis of many cancers, but its role in colorectal cancer (CRC) is still unknown. The purpose of our research is to clarify the role of SLC35A3 in the CRC. The expression level of SLC35A3 in CRC was evaluated by Tumor Immune Estimate Resource (TIMER), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and qRT-PCR experiment. TCGA data set was used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. An overall survival model was constructed and validated based on the expression level of SLC35A3 and the results of multivariate analysis. cBioPortal tool is used to analyze SLC35A3 mutation in CRC, and UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in CRC. In addition, the role of SLC35A3 in the CRC was determined by GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis and correlation analysis of immune checkpoints. Compared with adjacent normal tissues of CRC and colon epithelial cells , the expression of SLC35A3 in CRC tissues and CRC cell lines decreased. The low expression of SLC35A3 is related to N stage, pathological stage and lymph infiltration, and is not conducive to overall survival (OS) and disease specific survival (DSS). According to Receiver Operating Characteristic (ROC) analysis, SLC35A3 could be an important diagnostic biomarker for patients with CRC. The nomograph based on SLC35A3 is a model superior to a single prognostic factor. SLC35A3 has multiple types mutations in CRC, and its promoter methylation level is significantly reduced. GO and KEGG analysis display the SLC35A3 may involved in the transmembrane transporter activity, cell communication and the interaction of neural active ligand receptors. GSEA disclosed that SLC35A3 may participate in energy metabolism, DNA repair, cancer pathway. In addition, SLC35A3 is closely related to a variety of immune cell infiltration and immune checkpoint expression. The results of this study indicate that the decreased expression of SLC35A3 is closely related to poor prognosis of CRC and immune cell infiltration. SLC35A3 is a promising independent prognostic biomarker and a potential therapeutic target for CRC.