In smokers, the axis NCAPG/hsa-let-7b-5p/TMPO-AS1 promotes lung adenocarcinoma.

Background: Smoking is linked to high morbidity and mortality rates of lung cancer, emphasizing the need for a better understanding of prognosis-related mRNA/miRNA/lncRNA-ceRNA networks.

Materials and methods: The study utilized databases like OncoMX, The University of ALabama at Birmingham CANcer data (UALCAN), OncoDB, ENCORI, Kaplan-Meier (KM) Plotter, miRNet, CancerMIRNome, TISIDB, and TIMER2.0 to analyze NCAPG/miRNA and LncRNA expression in lung cancer tumors and healthy tissues.

Results: The NCAPG gene is overexpressed in lung cancer cells. High NCAPG expression is associated with adenocarcinoma patients with a log fold change of 8.7 in case of tumor vs. normal samples (t = 515, n = 59). Overexpression of NCAPG indicates poor overall survivability in lung adenocarcinoma (LUAD) patients [hazard ratio (HR) = 1.6, confidence interval (CI) = 1.34-1.9, p = 9.9e-08] and those with a smoking history (HR = 1.44, CI = 1.11-1.87, p = 0.0062), but not significantly associated with lung squamous cell carcinoma (LUSC). miRNA hsa-let-7b-5p negatively correlates (R = -0.348) with NCAPG expression, with its down expression associated with poor survivability (HR = 0.71), while lncRNA TMPO-AS1 positively correlates (R = 0.575) with the NCAPG axis, with its overexpression associated with poor survivability (HR = 2.16).

Conclusion: Elevated levels of NCAPG and TMPO-AS1 in lung adenocarcinoma patients lead to aggressive growth and poor prognosis. miRNA hsa-let-7b-5p, a key miRNA, may inhibit these factors, potentially improving patient prognosis. Further research and clinical trials are needed to validate this targeted therapy.