Affiliation:
1. Peritoneal Oncology Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100030, China
Abstract
Background:
Gastric cancer (GC) is the most common malignancy of the human digestive
system and represents the second leading cause of cancer-related deaths. As early GC is generally
mild or asymptomatic and advanced GC is commonly diagnosed, early detection has a significant
impact on clinical outcomes. This study aimed to identify epigenetic factors (EFs) as potential
GC biomarkers.
Methods:
We identified 3572 differential expressed genes (DEGs) from 436 GC tissues and 41
non-tumor adjacent samples through The Cancer Genome Atlas (TCGA) datasets. Among them, a
total of 57 overlapped genes were identified as differentially expressed EFs (DE-EFs), including 25
up-regulated DE-EFs and 32 down-regulated DE-EFs.
Results:
Then, Gene Ontology (GO) enrichment analysis revealed that the DE-EFs were mainly
associated with histone modification, chromatin remodeling, histone binding, modificationdependent
protein binding, etc. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG)
analysis results suggested that RNA degradation, thermogenesis, shigellosis, insulin resistance,
AMPK, and FoxO signaling pathways play roles in the progression of GC. Subsequently, Cox
regression and Kaplan-Meier analysis showed that higher expression levels of the three hub EFs,
including BRCC3, USP12, and WAC, were associated with better patients’ OS. We also found that
GC patients in the TCGA dataset with the earlier stage of TNM stage, invasion, depth of tumor,
lymph node metastasis, distant metastasis, and younger age had significantly better GC patients’
OS.
Discussion:
Furthermore, as the pathway enrichment analysis showed that BRCC3 participated in
NOD-like receptors (NLRs)-mediated signaling and the homologous recombination (HR) pathways,
strong and statistically significant positive relationships were found between BRCC3 with
genes in NLRs signaling and HR pathways, including BRCA1, BRCA2, Rad51, BRE, TOPBP1,
HSP90AA1, CASP1, NEK7, and SUGT1, respectively.
Conclusion:
We found three hub EFs, namely BRCC3, USP12, and WAC, which were downregulated
in GC tissues compared to normal tissues, associated with the overall survival of GC patients
and could be used as potential biomarkers to predict prognosis in GC patients. The regulation of
hub genes in GC may promote the exploration of the epigenetic mechanisms associated with tumorigenesis
and provide potential targets for GC diagnosis and treatment.
Funder
Beijing Haidian District Health Development Research and Cultivation Program
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine