Comprehensive analysis of acetylation-related genes for the prognosis and immunotherapy response of gastric cancer.

Abstract

38 Background: Although clinical researchers have made great progress in the treatment of gastric cancer, the overall survival time of gastric cancer patients remains unfavorable,It has been reported that HDAC1 is a prognostic marker for survival. However, the relationship between acetylation modification and the prognosis and treatment of gastric cancer has not been elaborated so far. Therefore, we carried out a systematic study and hope to provide novel therapeutic targets. Methods: We obtained the RNA sequencing data of GC patients and the corresponding clinical features from GEO database. T-test was performed to analyze the difference in expression of acetylation-related genes in normal and tumor samples from TCGA-STAD dataset.Using median expression as the threshold, univariate cox regression was performed to analyze the prognostic differences in overall survival (OS) for each acetylation-related gene. ssGSEA was utilized to analyze the percentage of infiltration of 28 immune cells in different clusters. Subsequently, we performed functional enrichment analysis of the differential genes using DAVID.used TIDE to analyze the effect of immune checkpoint inhibition. In addition, we compared the differences in TIDE scores across scoring subgroups. Results: By comparing 32 normal samples and 362 tumor samples in the TCGA dataset, we found that most acetylation-related genes are differentially expressed.most of the KAT genes were amplified more frequently than the deletion frequency, especially KAT2A and ESC1, while the deletion frequency of HDAC4 was high.CREBBP and KAT6A genes were mutated with high frequency.The results of acetylation-related gene clustering were divided into two subgroups (KAT-KDAC-cluster 1 and KAT-KDAC-cluster 2), Cluster 1 was mainly enriched in processes such as mismatch repair and homologous recombination during DNA replication, and cluster 2 was mainly enriched in calcium signaling, insulin signaling pathway and actin cytoskeleton regulation.We filtered out 9 genes most associated with GC were screened by random forest, and 2 of them were found to be unrelated to patient prognosis by univariate analysis, resulting in 7 genes, including FERMT2, CALD1, TGFBII, PPP1R14A, PPPIR3C, ADAMTS1, and RBPMS2.and KAT-KDAC scores were calculated.KAT-KDAC score group had lower TIDE scores, predicting better immune efficacy for patients in the low-KAT-KDAC score group. Conclusions: Expression of acetylation-related genes affects the prognosis of gastric cancer.