Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers.
Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers.
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DOI：
10.1042/cs20120240
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Yen Y
中科院分区：
文献类型：
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作者：
Liu X;Zhang H;Lai L;Wang X;Loera S;Xue L;He H;Zhang K;Hu S;Huang Y;Nelson RA;Zhou B;Zhou L;Chu P;Zhang S;Zheng S;Yen Y
RRM 2 [RR（核糖核苷酸还原酶）小亚基M2]的过表达显著增强癌细胞增殖和侵袭的能力。为了进一步研究RRM 2和CRC（结直肠癌）的相关性，我们将RRM 2的表达与CRC的临床结果相关联。对来自COH [（希望之城）国家医学中心，217例]和浙江大学（浙江大学，220例）的CRC进行回顾性结局研究。免疫组化法检测RRM 2蛋白表达水平，实时荧光定量PCR法进行验证。多变量logistic分析显示，在COH和ZJU集中，RRM 2-高的远处转移校正OR（比值比）分别为2.06 [95%CI（置信区间），1.01-4.30]和5.89（95%CI，1.51-39.13）。Kaplan-Meier分析显示RRM 2的高表达对两组CRC的OS（总生存期）和PFS（无进展生存期）均有显著的负面影响。多变量考克斯分析进一步表明，COH和ZJU集中RRM 2-高OS的HR（风险比）分别为1.88（95% CI，1.03-3.36）和2.06（95% CI，1.10-4.00）。分层分析显示，在COH集中的MMR（错配修复）基因缺陷亚组中，RRM 2的HR显著增加至12.22（95%CI，1.62-258.31）。同时，实时研究表明，通过siRNA（小干扰RNA）下调RRM 2可以显著和特异性地降低HT-29和HCT-8细胞的细胞生长和粘附能力。因此，RRM 2是一个独立的预后因素，并预测CRC的生存率差。它也是一个潜在的预测因素，用于识别CRC化疗的良好反应者。
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.