Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers

Abstract

The overexpression of RRM2 [RR (ribonucleotide reductase) small subunit M2] dramatically enhances the ability of the cancer cell to proliferate and to invade. To investigate further the relevance of RRM2 and CRCs (colorectal cancers), we correlated the expression of RRM2 with the clinical outcome of CRCs. A retrospective outcome study was conducted on CRCs collected from the COH [(City of Hope) National Medical Center, 217 cases] and ZJU (Zhejiang University, 220 cases). IHC (immunohistochemistry) was employed to determine the protein expression level of RRM2, and quantitative real-time PCR was employed to validate. Multivariate logistic analysis indicated that the adjusted ORs (odds ratios) of RRM2-high for distant metastases were 2.06 [95% CI (confidence interval), 1.01–4.30] and 5.89 (95% CI, 1.51–39.13) in the COH and ZJU sets respectively. The Kaplan–Meier analysis displayed that high expression of RRM2 had a negative impact on the OS (overall survival) and PFS (progress-free survival) of CRC in both sets significantly. The multivariate Cox analysis further demonstrated that HRs (hazard ratios) of RRM2-high for OS were 1.88 (95% CI, 1.03–3.36) and 2.06 (95% CI, 1.10–4.00) in the COH and ZJU sets respectively. Stratification analysis demonstrated that the HR of RRM2 dramatically increased to 12.22 (95% CI, 1.62–258.31) in the MMR (mismatch repair) gene-deficient subgroup in the COH set. Meanwhile, a real-time study demonstrated that down-regulation of RRM2 by siRNA (small interfering RNA) could significantly and specifically reduce the cell growth and adhesion ability in HT-29 and HCT-8 cells. Therefore RRM2 is an independent prognostic factor and predicts poor survival of CRCs. It is also a potential predictor for identifying good responders to chemotherapy for CRCs.

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

“…RRM2 is known to function as a tumor driver during carcinogenesis and high expressed in esophageal cancer, gastric cancer, colon cancer, and hepatocellular cancer [21][22][23][24][25]. This study also showed that RRM2 was higher expressed in most PTC samples and seemed to be more intensively stained in UTC tissues.…”

Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers

“…Antibodies against RRM2 and RRM2B were previously generated, selected and tested in our lab [23]. Antibodies against ER (Clone: SP1), PR (Clone: PgR636), HER2 (Clone: A0485) and Ki67 (Clone: MIB-1) were purchased from Dako company, and the p53 antibody (Clone: DO-7) was purchased from Vector Lab.…”

High Expression of Ribonucleotide Reductase Subunit M2 Correlates with Poor Prognosis of Hepatocellular Carcinoma

“…RRM2 depletion significantly reduced antiapoptotic protein Bcl-2 expression and RRM2 suppression led to increased Bcl-2 degradation 10. RRM2 was reported to play an active role in tumor progression11 and elevated RRM2 levels were correlated with poor prognosis for patients with colorectal cancer, pancreas adenocarcinoma, lung adenocarcinoma, and ovarian cancer 12–15. RRM2 was overexpressed in human HCC 16,17.…”