Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.
Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.
复制标题
核糖核苷酸还原酶小亚基M2B预测结直肠癌的生存更好。
DOI：
10.1158/0008-5472.can-11-0054
复制
发表时间：
2011-05-01
期刊：
影响因子：
11.2
通讯作者：
Yen Y
中科院分区：
文献类型：
--
作者：
Liu X;Lai L;Wang X;Xue L;Leora S;Wu J;Hu S;Zhang K;Kuo ML;Zhou L;Zhang H;Wang Y;Wang Y;Zhou B;Nelson RA;Zheng S;Zhang S;Chu P;Yen Y
核糖核苷酸还原酶亚基RRM 2B（p53 R2）已被报道抑制结直肠癌（CRC）的侵袭和转移。在这里，我们报告说，RRM 2B的高水平表达与显着更好的生存在CRC患者。在荧光标记的原位小鼠异种移植模型中，我们证实了相对于转移的对照细胞，RRM 2B在非转移性CRC细胞中的过表达防止了肺和/或肝转移。临床结局研究在具有103个CRC的训练集和具有220个CRC的验证集上进行。所有参与者都接受了手术，定期随访以确定生存率。采用新开发的特异性RRM 2B抗体进行免疫组织化学（IHC），以确定组织阵列上RRM 2B的表达水平。在训练集中，Kaplan-Meier和多变量考克斯分析显示RRM 2B与CRC的更好生存相关，尤其是在IV期患者中（风险比，HR=0.40; 95% CI 0.18-0.86，p=0.016）。在验证集中，RRM 2B与肿瘤侵袭（比值比，OR=0.45，95%CI 0.19-0.99，p=0.040）和淋巴结受累（OR=0.48，95%CI 0.25-0.92，p=0.026）呈负相关。此外，如通过多变量分析确定的，在该组中RRM 2B的表达升高与更好的预后相关（HR=0.48，95%CI 0.26-0.91，p=0.030）。进一步的研究表明，RRM 2B与晚期III-IV期肿瘤而不是早期I-II期肿瘤的CRC的更好生存相关。综上所述，我们的研究结果证实RRM 2B抑制癌细胞的侵袭性，并且其表达与CRC患者更好的生存预后相关。
Ribonucleotide reductase subunit RRM2B (p53R2) has been reported to suppress invasion and metastasis in colorectal cancer (CRC). Here we report that high levels of RRM2B expression is correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in non-metastatic CRC cells prevented lung and/or liver metastasis, relative to control cells that did metastasize. Clinical outcome studies were conducted on a training set with 103 CRCs and a validation set with 220 CRCs. All participants underwent surgery with periodic follow-up to determine survivability. A newly developed specific RRM2B antibody was employed to perform immunohistochemistry (IHC) for determining RRM2B expression levels on tissue arrays. In the training set, the Kaplan-Meier and multivariate COX analysis revealed that RRM2B is associated with better survival of CRCs, especially in stage IV patients (Hazard ratio, HR=0.40; 95% CI 0.18–0.86, p=0.016). In the validation set, RRM2B was negatively related to tumor invasion (odds ratio, OR=0.45, 95% CI 0.19–0.99, p=0.040) and lymph node involvement (OR=0.48, 95% CI 0.25–0.92, p=0.026). Further, elevated expression of RRM2B was associated with better prognosis in this set as determined by multivariate analyses (HR=0.48, 95% CI 0.26–0.91, p=0.030). Further investigations revealed that RRM2B was correlated with better survival of CRCs with advanced stage III–IV tumors rather than earlier stage I–II tumors. Taken together, our findings establish that RRM2B suppresses invasiveness of cancer cells and that its expression is associated with a better survival prognosis for CRC patients.