TMEM171 Is a Potential Biomarker Associated with Lung Injury and Lung Adenocarcinoma

Background Lung cancer therapy frequently induces lung injury, leading to treatment interruption and poor prognosis; however, specific biomarkers linking cancer therapy and therapy-related lung injury remain poorly defined. This study aimed to identify a biomarker relevant to both lung cancer progression and lung injury, with emphasis on prognostic significance and immune infiltration.

Methods RNA-sequencing data from Gene Expression Omnibus (GEO) (GSE166340, GSE27128) were used to identify lung injury-related genes, and The Cancer Genome Atlas (TCGA) data were analyzed to evaluate their expression in lung adenocarcinoma (LUAD). Single-cell RNA-sequencing data (PRJNA846488) and in vivo lung injury models were used to validate TMEM171 expression. Prognostic value was assessed using Kaplan–Meier analysis, univariate and multivariate Cox regression, and a least absolute shrinkage and selection operator (LASSO) prognostic model. Immune infiltration, immune checkpoint correlations, and pathway enrichment were analyzed using single-sample gene set enrichment analysis (ssGSEA). Functional effects of TMEM171 were examined by in vitro knockdown experiments.

Results A total of 10 lung injury-related genes were identified. TMEM171 was significantly upregulated in LUAD tissues and immunotherapy-induced lung injury models. High TMEM171 expression was an independent predictor of poor prognosis and was associated with TP53 mutations, apoptosis, and inflammatory response pathways. TMEM171 expression positively correlated with neutrophil infiltration and immune checkpoint expression. TMEM171 knockdown suppressed malignant behavior of LUAD cells and induced G1/S cell-cycle arrest in vitro.

Conclusions TMEM171 represents a potential biomarker linking lung adenocarcinoma and therapy-related lung injury and may serve as a candidate for future mechanistic investigation.