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.

Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations

“…AFF3 encodes tissue‐restricted nuclear transcriptional activator that binds to the enhancer region of genes. It involved in the immune response and is associated with gastric and breast cancer 19,20 . SRCAP is involved in chromatin remodeling and transcription activation.…”

“…It involved in the immune response and is associated with gastric and breast cancer. 19,20 SRCAP is involved in chromatin remodeling and transcription activation.…”

Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential

“…Some of the ZFPs identified so far may be oncogenes or tumor suppressors in GC progression, and researchers have designed specific ZFPs to regulate the expression of the corresponding target genes in mammals, which have made great progress [206]. In light of the high intertumoral, intratumoral and interpatient heterogeneity of GC, accurate classification and stratification via reference indicators are indispensable for the diagnosis, treatment and prognosis of GC [207][208][209]. With the in-depth development of bioinformatics for discovering more ZFPs and the elucidation of their molecular mechanisms, staging based on various ZFPs can facilitate more optimized early diagnosis and personalized therapeutics for GC.…”

Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

“…Recent studies have demonstrated that specific key genes can impact the immune microenvironment of tumors, thereby affecting tumor immunotherapy. For example, UHRF1 in hepatocellular carcinoma (HCC) 19 , CXCL11 in colorectal cancer (CRC) 20 , AFF3 in GC 21 , and so on. In the current study, we observed a significant upregulation of TIE1 in GC which is associated with a poor prognosis for patients.…”