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.
Highlights
Gastric cancer (GC) is known as a gastrointestinal malignance with dismal clinical outcome and shows increasing incidence and mortality worldwide.[1]
We found that high-risk Transcriptional factors (TFs) were associated with activation of cancer-related signaling and tumor microenvironment (TME) remodeling, especially in mesenchymal component accumulation and stromal cell infiltrating
We precisely demonstrated a quantified TME infiltration pattern remodeling by TFs and found HEYL could represent a potentially prognostic and therapeutic target in gastric cancer
Summary
Gastric cancer (GC) is known as a gastrointestinal malignance with dismal clinical outcome and shows increasing incidence and mortality worldwide.[1]. A large amount of works suggested the vital roles of TME formation or transition in tumor progression and therapeutic response.[6,7] the diverse stromal components such as fibroblasts and mesenchymal stromal cells could serve as the mediators for tumor stromal cells intensive communications and coordinate the construction of tumorigenic microenvironment.[8]. We systematically curated the TFs prognostic risks and correlated their characteristics on GC-TME heterogeneity by investigating the TCGA-STAD transcriptional profiles. We found that high-risk TFs were associated with activation of cancer-related signaling and TME remodeling, especially in mesenchymal component accumulation and stromal cell infiltrating. We found HEYL enhances gastric carcinogenesis through activating oncogenic signaling pathways and regulating CDH11 expression under DNA level in GC cells. We precisely demonstrated a quantified TME infiltration pattern remodeling by TFs and found HEYL could represent a potentially prognostic and therapeutic target in gastric cancer
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