Prognostic and therapeutic importance of TROP-2 and MUC-1 in non-small cell lung cancer: A systematic review and meta-analysis.

Non-small cell lung cancer (NSCLC) represents ~85% of all lung cancer and is a leading cause of cancer-related mortality worldwide. Trophoblast cell surface antigen-2 (TROP-2) and mucin-1 (MUC-1) have emerged as potential prognostic biomarkers and therapeutic targets. There are no reports of their combined impact as a biomarker in NSCLC. The present systematic review/meta-analysis aimed to evaluate the expression patterns and prognostic implications of TROP-2 and MUC-1 in NSCLC. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Population, Intervention, Comparison, and Outcome framework, 1,297 publications between 2019 and 2024 were systematically retrieved from PubMed, Scopus and EMBASE databases. A total of 12 studies (three for TROP-2 and nine for MUC-1) met the inclusion criteria and five (two for TROP-2 and three for MUC-1) were finally included in the final meta-analysis using fixed-effect models involving 1,159 patients. High TROP-2 [hazard ratio (HR) 1.43, 95% confidence interval (CI): 1.15-1.79; P=0.002] and MUC-1 (HR 2.25; 95% CI: 1.57-3.23, P<0.0001) were consistently overexpressed in NSCLC patient tissues. An exploratory pooled analysis of both biomarker groups demonstrated a significant association with poor clinical outcomes and short survival (HR 1.62; 95% CI: 1.34-1.96; P<0.00001), though this should not be interpreted as evidence of a true dual-biomarker effect. Mechanistically, both markers promote cancer cell proliferation, epithelial-mesenchymal transition, immune evasion and treatment resistance. In conclusion, TROP-2 and MUC-1 are valuable prognostic biomarkers in NSCLC. Their overexpression correlates with poor survival, supporting the development of targeted therapies in NSCLC.