Multiomics Integrated Analysis Identifies SLC24A2 as a Potential Link between Type 2 Diabetes and Cancer

Abstract

Background. So far, type 2 diabetes (T2D) is considered as an independent risk factor for various cancers, but the underlying mechanism remains unclear. Methods. SLC24A2 was first identified as a key gene strongly associated with fasting plasma glucose (FPG). Then, overlapped differentially expressed genes (DEGs) between T2D verse control and SLC24A2-high verse SLC24A2-low were extracted and imported into weighted correlation network analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for functional enrichment analysis of DEGs. Least absolute shrinkage and selection operator was utilized to build a T2D prediction model. Timer and K-M plotters were employed to find the expression and prognosis of SLC24A2 in pan cancer. Results. Interestingly, both DEGs between T2D verse control and SLC24A2-high verse SLC24A2-low enriched in cancer-related pathways. Moreover, a total of 3719 overlapped DEGs were divided into 8 functional modules. Grey module negatively correlated with T2D and FPG and was markedly involved in ribosome biogenesis. Ten SLC24A2-related genes (RRP36, RPF1, GRWD1, FBL, EXOSC5, BCCIP, UTP14A, TWISTNB, TBL3, and SKIV2L) were identified as hub genes, based on which the LASSO model accurately predicts the occurrence of T2D (AUC=0.841). In addition, SLC24A2 was only expressed in islet β cells and showed abnormal expression in 17 kinds of cancers and significantly correlated with the prognosis of 10 kinds of cancers. Conclusion. Taken together, SLC24A2 may link T2D and cancer by influencing the ribosome function of islet β cells and play different prognostic roles in different cancers.