In-silico analysis of CEP55/E2F1/hsa-let-7b-5p/TMPO-AS1 axis-based ceRNA network promoting poor prognosis in lung adenocarcinoma smokers

Abstract

Introduction: Smoking causes severe lung adenocarcinoma. High CEP55 expression correlates with clinico-pathological features, suggesting the mRNA/miRNA/lncRNA-ceRNA network’s crucial to prognosis.
Methods: The study used databases like TIMER 2.0, UALCAN, OncoMX, GEPIA2, OncoDB, ENCORI, KM Plotter, TNMplot, CancerSEA, CellTracer, GENI, Intogen, miRNet, TISIDB, GSCA, the Enrichr, HDOCK, and LigPlot databases to analyze CEP55 and associated ceRNA expression in lung cancer tumors and normal tissues.
Results: The CEP55 gene is overexpressed in both lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD). Findings suggested that overexpression of CEP55 has a poor prognosis in terms of overall survival (OS) (HR = 1.63, CI = 1.44–1.84, P = 1.4e-15), first progression (FP) (HR = 1.81, CI = 1.52–2.15, P = 6.4e-12), and post-progression survival (PPS) (HR = 1.141, CI = 1.14–1.74, P = 00012). Particularly, high CEP55 expression is significantly associated with OS + LUAD patients (HR = 1.55, CI = 1.3-1.84, P = 7.2e-07) and those with OS + LUAD smokers (HR = 1.49, CI = 1.15-1.94, P = 0.0026). The study found a strong link between lncRNA-TMPO-AS1 overexpression and poor prognosis in LUAD + smokers, and hsa-let-7b-5p downexpression was associated with poor survival in LUAD. The least binding energy or most favourable interaction score between hsa-let-7b-5p and CEP55 was found to be -124.52 kcal/mol.
Conclusion: Smokers with lung adenocarcinoma had worse prognoses due to higher E2F1, CEP55, and TMPO-AS1 levels. Also, TMPO-AS1 sponge formation with hsa-let-7b-5p may be the cause of this feedback loop.

Keywords: CEP55, Lung adenocarcinoma, ceRNA Network, Prognosis, Smokers