Identification of Prognosis Signature and Analysis of the Immune Microenvironment in Gastric Cancer Based on ALKBH5

Abstract Background N6-methyladenosine(m6A) RNA regulators play important roles in cancers, but the functions and mechanism of them have not been demonstrated clearly in gastric cancer (GC). Methods In this study, the GC samples with clinical information and RNA transcriptome were downloaded from TCGA database. The different expression genes were compared by absolute value and median ± standard deviation (sd). Samples with complete information were randomly divided into training dataset and test datasets. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in training dataset and constructed a risk model by Cox and LASSO regression. The model was testified in test datasets, the overall survival (OS) was compared with Kaplan-Meier method and immune cells infiltration was calculated by CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. Results ALKBH5 was the only one regulator whose expression was lower in tumor samples than that in normal samples, there was the same phenomenon in GEO dataset GSE29998. Low expression of ALKBH5 led to poor overall survival of GC patients and seemed to be an independent protective factor. The model based on ALKBH5 regulated genes was validated in both two datasets (training/test) and it displayed potential capacity to predict clinical prognosis. Gene Ontology (GO) analysis implied that the DEGs were involved in immune response, CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. Conclusions In this study we found that ALKBH5 might be a suppressor of GC, ALKBH5 and its related genes were latent biomarkers and immunotherapy targets.