Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Biosci Rep. 2021 Jul 30;41(7):BSR20210055. doi: 10.1042/BSR20210055.

Abstract

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from GSE15459, GSE22377, GSE51105, GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.

Keywords: Early B-cell factors; cell cycle; gastric cancer; immune; immunotherapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Antimetabolites, Antineoplastic / therapeutic use
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Clinical Decision-Making
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism
  • Tumor Microenvironment / genetics*
  • Tumor Microenvironment / immunology

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Histone Deacetylase Inhibitors
  • Immune Checkpoint Inhibitors