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.
Highlights
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 [1]
A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort was enrolled from The Cancer Genome Atlas (TCGA) project, data of transcription profiling, genetic alterations and methylation (Methylation450k) for early B-cell factor (EBF) were all obtained from TCGA project
Based on the single-sample gene set enrichment analysis (ssGSEA) of the infiltration of 28 immunocytes, we revealed that the increased abundance of several immunocytes in the tumor microenvironment, including activated CD4 T cells, activated dendritic cells, CD56dim natural killer cell, γδ T cells, memory B cell, and natural killer T cell, while the infiltration of other types decreased in tumor tissue, including activated B cell, CD56bright natural killer cell, effector memory CD4 T cell, eosinophil, immature dendritic cell, mast cell, and neutrophil
Summary
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 [1]. The clinical symptoms for GC patients are not significant in the early stage, most patients are diagnosed at the advanced tumor stage, which leads to a 5-year survival as low as ∼10% [6]. Intestinal type is mostly diagnosed in patients older than 70 years, along with a better prognosis [8,9]. The diffuse type often occurs in younger women, with a poor prognosis [9]. After reviewing 18441 GC patients, Zhao et al [11] revealed that the independent risk factors for poor overall survival (OS) are old age, weight loss, smoking history, and process to advanced tumor stage. Minami et al [12] found that among patients who underwent curative resection, ever-smoking, earlier age started smoking are tightly associated with the cancer-related deaths of GC; lifestyle adjustment could improve survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
