TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

• Published in: International immunopharmacology Vol. 84; p. 106532
• Main Authors: Yang, BoWen, Bai, Jin, Shi, Ruichuan, Shao, Xinye, Yang, Yujing, Jin, Yue, Che, Xiaofang, Zhang, Ye, Qu, Xiujuan, Liu, Yunpeng, Li, Zhi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2020; Elsevier BV
• Subjects: Aged; Base excision repair; Biomarkers, Tumor - immunology; Cancer; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA repair; Enrichment; Epithelial-Mesenchymal Transition; Female; Functional analysis; Gastric cancer; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Growth factors; Helper cells; Humans; Immune checkpoint; Immune checkpoint blockade; Immune infiltration; Immune system; Male; Mesenchyme; Mismatch repair; Mutation; Prognosis; Repair; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; Stomach Neoplasms - mortality; TGFB2; Transforming Growth Factor beta2 - immunology; Transforming growth factor-b; Tumor mutation burden; Tumor-infiltrating lymphocytes; Tumors; Epithelial-mesenchymal transition; TGFB2; Immune checkpoint blockade; Gastric cancer; Tumor mutation burden; Immune infiltration
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106532

•Overexpression of TGFB2 was positively associated with EMT status and negatively with TMB levels in gastric cancer.•TGFB2 in gastric cancer was co-expressed with neurite-related genes that may drive EMT.•Tumor-infiltrating immune cells might participate in the process of TGFB2 affecting TMB levels in gastric cancer. Immune checkpoint blockade (ICB) has been a major breakthrough in various cancers including gastric cancer (GC), yet the clinical outcomes remain poor. Currently, epithelial-mesenchymal transition (EMT) has been reported to be associated with tumor mutational burden (TMB), which can cause lack of response to ICB. However, the underlying mechanism remains unknown. Members of the transforming growth factorβ (TGFB) family are regarded as the main mediators of EMT, yet how TGFB2 drives EMT in GC is not fully understood. In this study, we found that overexpression of TGFB2 was correlated with poor prognosis in TGCA-STAD and four GEO GC datasets.Gene set enrichment analysis revealed that the EMT pathway was significantly enriched in the high TGFB2 expression group, whilst the TMB-related pathways including mismatch repair, base excision repair, and DNA replication were strongly enriched in the low expression group. Furthermore, EMT score analysis, WGCNA and functional analysis showed that TGFB2 was co-expressed with neurite-related pathways that might drive EMT. Also, CIBERSORT analysis revealed that tumor-infiltrating immune cells like T follicular helper cells might participate in the process of TGFB2 affecting TMB levels in GC. Moreover, in other various cancers, TGFB2 was also negatively correlated with TMB levels as well as ICB response. Overall, these results revealed that TGFB2 could play a vital role in linking EMT and TMB in GC, suggesting that TGFB2 may be a predictive therapeutic target for GC.