Prognostic significance of the TMPO-AS1/ hsa-let-7b-5p axis and nTreg infiltration in lung adenocarcinoma: an in silico analysis

Abstract

While several G2/M oncogenes are known to promote tumor progression, their coordinated tumor-suppressive networks antagonizing this axis and their regulatory and immunological contexts remain poorly defined. We performed a multi-layered integrative analysis combining correlation profiling (UALCAN and ENCORI), multi-endpoint survival analysis (KM Plotter: OS, FPS, PPS across pan-lung, LUAD, and smoker cohorts), and transcriptomic refinement using TNMplot. A miRNA–mRNA regulatory network was constructed via miRNet, refined using UALCAN expression filtering, KM survival, and CancerMIRNome ROC analysis, followed by ENCORI-based miRNA–gene correlation. Direct miRNA–mRNA and lncRNA–miRNA binding affinities were assessed using IntaRNA. lncRNAs associated with the key miRNA were identified via Enrichr, filtered by expression, correlation, and survival, and validated by binding and gene correlation analyses. Finally, immune cell correlations were evaluated using GSCA, and an integrated ROC model was generated in R. We identified a high-confidence panel of six tumor suppressors (CBX7, CD81, CRY2, CYBRD1, NR3C2, REEP5) and six G2/M oncogenes (AURKA, AURKB, BUB1, FOXM1, MELK, TTK) based on correlation, survival, and TNMplot criteria. hsa-let-7b-5p emerged as a central regulatory miRNA (AUC = 0.89) positively correlated with tumor suppressors and predicted to bind all six oncogenes. TMPO-AS1 was identified as an oncogenic lncRNA antagonizing hsa-let-7b-5p via strong binding (–15.85 kcal/mol) and negative correlation with tumor suppressors. An integrated lncRNA-miRNA-mRNA ROC model achieved an AUC ≈ 0.97. Immune analysis revealed reciprocal patterns: tumor suppressors correlated with MAIT, NKT, and Tfh cells and inversely with exhausted cells and nTregs, whereas oncogenes showed the opposite trend with the same. This study defines a robust G2/M -associated regulatory framework in LUAD, characterized by reciprocal dysregulation of oncogenes and tumor suppressors and associated with the predicted TMPO-AS1–hsa-let-7b-5p regulatory network, which is linked to a less immunosuppressive tumor microenvironment, offering potential prognostic and therapeutic implications in LUAD.