title: 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.
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute, City of Hope National Comprehensive Cancer Center, Duarte, CA 91010-3000, USA.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Lily
authors.initials: L
authors.lastname: Lai
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Sofia
authors.initials: S
authors.lastname: Loera
authors.forename: Lijun
authors.initials: L
authors.lastname: Xue
authors.forename: Huiyin
authors.initials: H
authors.lastname: He
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Shuya
authors.initials: S
authors.lastname: Hu
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Huang
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Nelson
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Lun
authors.initials: L
authors.lastname: Zhou
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.forename: Suzhan
authors.initials: S
authors.lastname: Zhang
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D009362:Neoplasm Metastasis / Q000473:pathology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012189:Retrospective Studies; D012262:Ribonucleoside Diphosphate Reductase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase