Charactering tumor microenvironment reveals stromal‐related transcription factors promote tumor carcinogenesis in gastric cancer

Abstract

Abstract Transcription factors represent the crucial role of controlling gene transcription in cancer development and progression. However, their functions in gastric cancer have not been thoroughly characterized. For this study, we comprehensively evaluated the correlation between infiltration patterns of tumor microenvironment (TME) cells and TFs expression in the cohort of stomach adenocarcinoma (STAD) from TCGA database. We integrally explored differential expression panel and prognostic value of candidate TFs in TCGA‐STAD cohort. Notably, we found a key transcription factor named HEYL, which its expression level was correlated with stromal component transformation of TME. HEYL was regularly high expressed in gastric cancer and correlated with patients’ poor prognosis. Knockdown of HEYL prominently abrogated the tendency of cell proliferation, migration, and progression in gastric cancer. Consistently, overexpression of HEYL strikingly accelerated the gastric carcinoma development through activating oncogenic signaling pathways and transcriptional activation of cadherin 11 (CDH11). Our findings not only identified the close relationship between TFs and TME phenotype, but also emphasized the crucial importance of TFs, especially HEYL, which could be identified as a candidate biomarker to evaluate prognostic risk and therapeutic effect in gastric cancer.

Keywords

• CDH11
• gastric cancer
• HEYL
• transcriptional factors
• tumor microenvironment