1. Epigenetically regulated gene expression profiles decipher four molecular subtypes with prognostic and therapeutic implications in gastric cancer.
- Author
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Weng, Siyuan, Li, Minghao, Deng, Jinhai, Xu, Hui, Ren, Yuqing, Zhou, Zhaokai, Wang, Libo, Zhang, Yuyuan, Xing, Zhe, Li, Lifeng, Liu, Zaoqu, and Han, Xinwei
- Subjects
PROGNOSIS ,PACLITAXEL ,GENE expression profiling ,STOMACH cancer ,RECEPTOR for advanced glycation end products (RAGE) ,GENETIC regulation ,APATINIB - Abstract
Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract which seriously endangers the health of human beings worldwide. Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of GC. This study aimed to investigate the impact of epigenetically regulated genes on the prognosis, immune microenvironment, and potential treatment of GC. Results: Under the premise of verifying significant co-regulation of the aberrant frequencies of microRNA (miRNA) correlated (MIRcor) genes and DNA methylation-correlated (METcor) genes. Four GC molecular subtypes were identified and validated by comprehensive clustering of MIRcor and METcor GEPs in 1521 samples from five independent multicenter GC cohorts: cluster 1 was characterized by up-regulated cell proliferation and transformation pathways, with good prognosis outcomes, driven by mutations, and was sensitive to 5-fluorouracil and paclitaxel; cluster 2 performed moderate prognosis and benefited more from apatinib and cisplatin; cluster 3 was featured by an up-regulated ligand–receptor formation-related pathways, poor prognosis, an immunosuppression phenotype with low tumor purity, resistant to chemotherapy (e.g., 5-fluorouracil, paclitaxel, and cisplatin), and targeted therapy drug (apatinib) and sensitive to dasatinib; cluster 4 was characterized as an immune-activating phenotype, with advanced tumor stages, benefit more from immunotherapy and displayed worst prognosis. Conclusions: According to the epigenetically regulated GEPs, we developed four robust GC molecular subtypes, which facilitated the understanding of the epigenetic mechanisms underlying GC heterogeneity, offering an optimized decision-making and surveillance platform for GC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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