Abstract
Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods: RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results: RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.
Highlights
Breast cancer is the most frequently diagnosed tumor and a leading cause of cancer-related deaths among women worldwide [1]
Our analysis revealed that Ribonucleotide reductase M2 subunit (RRM2) was significantly higher expressed in male breast carcinoma, intraductal cribriform breast adenocarcinoma, invasive breast carcinoma, invasive lobular breast carcinoma, invasive ductal breast carcinoma, ductal breast carcinoma in situ, invasive ductal breast carcinoma epithelia, and ductal breast carcinoma, compared with the corresponding normal tissues (Figure 2A–H and Table 1)
We found that RRM2 was strongly elevated in basal-like subtype with respect to non-basal-like subtype; the same pattern of change was observed in triple-negative breast cancer (TNBC) patients (Figure 3H,I and Table 2)
Summary
Breast cancer is the most frequently diagnosed tumor and a leading cause of cancer-related deaths among women worldwide [1]. Ribonucleotide reductase M2 subunit (RRM2), a rate-limiting enzyme for DNA synthesis and repair, displays vital roles in many critical cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, and senescence [3]. Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. The prognostic significance of RRM2 gene in breast cancer remains to be investigated. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. The Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis
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