Na+/H+-Exchanger Family As Novel Prognostic Biomarkers In Colorectal Cancer

Abstract Background: The acidic characteristics of the tumor microenvironment (TME) are attributed to cancer cells’ needs of metabolism that produce a large amount of H+. In order not to affect its own life activities, it needs to release H+ into the intercellular space through an efficient Na+/H+ exchanger. On account of the intestine whose physiological function is highly dependent on intestinal pH value, NHE family members may play a critical role in the occurrence and development of colorectal cancer (CRC).Methods: TCGA, GEPIA2, ONCOMINE, UALCAN, STRING, TIMER, Cytoscape, TargetScan, ENCORI, LncBase v.2, DNMIVD, HPA and CellMinerTM databases were used in our study.Results: The mRNA expression of SLC9A1, SLC9A2, SLC9A3 and SLC9A9 were evidently lower in COAD compared to normal samples, however, mRNA expression of SLC9A5, SLC9A8 and SLC9B2 were higher. Besides, mRNA expression of NHE family were extremely associated with clinicopathological features, tumor immune microenvironment and stemness score, DNA methylation and patient prognosis in COAD. Moreover, we conjectured that NHE family may play a role through MAPK or ErbB signaling pathway according to the results of GO/KEGG enrichment analysis. At last, we found that NHE family members were key factors of various kinds of cancers.Conclusion: Our study indicated that NHE family was new diagnostic and therapeutic targets for CRC, which could have important significance for the clinical treatment of CRC.