SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

Xu-Sheng Liu; Jian-Wei Yang; Jing Zeng; Xue-Qin Chen; Yan Gao; Xue-Yan Kui; Xiao-Yu Liu; Yu Zhang; Yao-Hua Zhang; Zhi-Jun Pei

doi:10.3389/fcell.2022.853596

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

Front Cell Dev Biol. 2022 Mar 24:10:853596. doi: 10.3389/fcell.2022.853596. eCollection 2022.

Authors

Xu-Sheng Liu¹, Jian-Wei Yang², Jing Zeng³, Xue-Qin Chen⁴, Yan Gao¹, Xue-Yan Kui¹, Xiao-Yu Liu¹, Yu Zhang¹, Yao-Hua Zhang¹, Zhi-Jun Pei^{1

5}

Affiliations

¹ Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
² Department of Nuclear Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
³ Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁴ Hubei University of Medicine, Shiyan, China.
⁵ Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Abstract

Background: Overexpression of solute carrier family 2 member 1 (SLC2A1) promotes glycolysis and proliferation and migration of various tumors. However, there are few comprehensive studies on SLC2A1 in colorectal cancer (CRC). Methods: Oncomine, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to analyze the expression of SLC2A1 in pan-cancer and CRC and analyzed the correlation between SLC2A1 expression and clinical characteristics of TCGA CRC samples. The expression level of SLC2A1 in CRC was certified by cell experiments and immunohistochemical staining analysis. The Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses of SLC2A1 relative genes were completed by bioinformatics analysis. The correlation between SLC2A1 expression level and CRC immune infiltration cell was analyzed by Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and TCGA database. The correlation between SLC2A1 expression level and ferroptosis and m6A modification of CRC was analyzed by utilizing TCGA and GEO cohort. Finally, the possible competing endogenous RNA (ceRNA) networks involved in SLC2A1 in CRC are predicted and constructed through various databases. Results: SLC2A1 is highly expressed not only in CRC but also in many other tumors. ROC curve indicated that SLC2A1 had high predictive accuracy for the outcomes of tumor. The SLC2A1 expression in CRC was closely correlated with tumor stage and progression free interval (PFI). GO, KEGG, and GSEA analysis indicated that SLC2A1 relative genes were involved in multiple biological functions. The analysis of TIMER, GEPIA, and TCGA database indicated that the SLC2A1 mRNA expression was mainly positively associated with neutrophils. By the analysis of the TCGA and GEO cohort, we identified that the expression of SLC2A1 is closely associated to an m6A modification relative gene Insulin Like Growth Factor 2 MRNA Binding Protein 3 (IGF2BP3) and a ferroptosis relative gene Glutathione Peroxidase 4 (GPX4). Conclusion: SLC2A1 can be used as a biomarker of CRC, which is associated to immune infiltration, m6A modification, ferroptosis, and ceRNA regulatory network of CRC.

Keywords: SLC2A1; ceRNA; colorectal cancer; immune infiltration; m6A modification.