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

Abstract

Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 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 RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 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 RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues ( p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs . T1: OR = 1.88, p = 0.001; N2 vs . N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 ( p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 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 RRM2 . RRM2 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 RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.

Identification of candidate biomarkers correlated with poor prognosis of breast cancer based on bioinformatics analysis

“…Ribonucleotide reductase M2 subunit (RRM2), a rate-limiting enzyme involved in DNA synthesis and damage repair, plays important roles in many cellular processes such as cell growth, invasiveness, migration and senescence et al [65]. RRM2 as a tumor driver is frequently overexpressed in various malignancies [66][67][68]. Others found that the expression level of RRM2 was correlated with invasion, cell differentiation, and metastasis in colorectal carcinoma [69], and correlated with lung cancer grade level [70].…”

Study on the effects of Polyphyllin I and Curcumin on liver cancer based on the cross-action of ferroptosis and energy metabolism

“…Current research reports that RRM2 is relatively highly expressed in breast cancer [17,18], lung adenocarcinoma (LUAD) [19,20], and cervical cancer [21,22], and it is also expressed in a variety of tumor cell proliferations. It plays an important role in the process of invasion, invasion and migration.Src kinase is the main product of the proto-oncogene c-Src and is a non-receptor tyrosine protein kinase.…”

Differences in Gene Expression Between High- and Low-Grade Serous Ovarian Cancers: Implications for Diagnosis and Prognosis

“…Yang et al recently revealed that RRM2 may prevent iron death in liver cancer and can be utilized as a tumor biomarker (34). In patients with lung adenocarcinoma, two investigations by Jin et al and Ma et al highlighted that the elevated RRM2 expression can be an independent predictor for poor prognosis (35,36). Through bioinformatics study, Shen et al discovered that RRM2 is substantially negatively associated with clinical staging in OC and that it represents an anticancer therapeutic target for patients with OC.…”