High expression of RRM2 as an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.

Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of in patients with LUAD was much higher than that in normal tissues ( = 3.99e-32). High expression of was significantly associated with tumor stage (IV I: OR = 3.02, = 0.012) and TNM classification (T2 . T1: OR = 1.88, = 0.001; N2 . N0: OR = 2.69, < 0.001). Kaplan-Meier survival analysis showed that high expression of was associated with a worse prognosis of LUAD compared low expression of ( = 7.86e-04). Multivariate analysis showed that high expression was an independent factor affecting overall survival (HR = 1.29, < 0.001). The association between gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of . over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.