AFF3 is a novel prognostic biomarker and a potential target for immunotherapy in gastric cancer

Abstract

Background: Gastric cancer (GC) is one of the most common cancers worldwide with a poor prognosis. The tumor microenvironment (TME) serves a pivotal role in affecting the prognosis and efficacy of immunotherapy. Given the poor prognosis of GC patients and the limitation of immunotherapy, we urged to identify new prognostic and immunotherapeutic biomarkers.

Methods: The transcriptome data were downloaded from the TCGA, GEO, and GEPIA databases, and performed differential analysis of AFF3 in tumor samples and normal samples. The UALCAN, Kaplan-Meier plotter and GEPIA databases were employed to assess the correlation of AFF3 with clinicopathological characteristics and prognosis. The potential mechanism of AFF3 was explored by the GO and KEGG enrichment. The potential role of AFF3 on tumor-infiltrating immune cells (TIICs) was explored by TIMER2.0 and TISIDB. TIMER2.0 and SangerBox3.0 databases were, respectively, used to determine the correlation of AFF3 with immune checkpoint (ICs), tumor mutational burden (TMB), and microsatellite instability (MSI) in GC.

Results: We found significant downregulation of AFF3 in GC tissues as compared with normal tissues. However, GC patients having a higher expression of AFF3 were found to have worse clinicopathological characteristics and prognosis. Moreover, the GO enrichment analysis illustrated that AFF3 might regulate the immune cells in the TME. In addition, the AFF3 was positively correlated with TIICs, ICs, TMB, and MSI.

Conclusion: Here, we conclude that AFF3 may be a promising potential marker for the diagnosis and prognosis of GC patients, and may influence response to ICIs by affecting TIICs and ICs expression in the TME.

Keywords: AFF3; bioinformatic analysis; gastric cancer; immunotherapy; prognosis.