TRIM29 is implicated in cancer progression; however, its function in lung adenocarcinoma (LUAD) remains unknown. We assessed the contribution of TRIM29 to LUAD biology, its influence on the tumor microenvironment (TME), and its prognostic relevance in LUAD. We analyzed two independent LUAD transcriptomic cohorts. Gene set enrichment analysis (GSEA) was performed using deconvolution-based TME profiling with xCell, ESTIMATE, and EPIC. Associations between TRIM29 and epithelial–mesenchymal transition (EMT), angiogenesis, stromal remodeling, and survival were corroborated using immunohistochemistry, histopathology, and cell line assays. Drug sensitivity analyses were performed to identify therapeutic agents for TRIM29-high tumors. GSEA consistently showed enrichment of EMT in TRIM29-high tumors across both mRNA datasets. Deconvolution revealed that TRIM29-high tumors harbored an increased number of fibroblasts and endothelial cells, along with elevated stromal scores. The GSEA and deconvolution results using the TRIM29-associated transcriptional module were consistent with those obtained from the single-gene analysis. In an independent cohort, immunohistochemistry and histopathology confirmed positive correlations between TRIM29 expression and SNAIL, TWIST, microvessel density, and stromal proportion. High TRIM29 expression at the transcript and protein levels is associated with poor overall survival. Functionally, TRIM29 inhibition in cell lines decreased N-cadherin, SNAIL, and TWIST expression while increasing E-cadherin expression. Drug response profiling revealed that mTOR inhibitors exhibited the highest activity in TRIM29-high cells. To our knowledge, this study provides evidence suggesting that TRIM29 may be associated with EMT-related transcriptional programs, angiogenesis, and stromal remodeling in LUAD, as well as with adverse clinical outcomes. An integrated pathology-transcriptome-outcome framework supports biomarker-guided strategies for TRIM29-high tumors, with mTOR inhibition emerging as a promising therapeutic strategy.
Hwang et al. (Sun,) studied this question.