Abstract 4183: Ribonucleotide reductase small subunit M2B associates with better survival of colorectal cancers through inhibiting tumor invasion and metastasis

Previous studies have demonstrated that RRM2B suppresses the invasion and metastasis of cancer cells. Here, we examined the hypothesis that RRM2B may be related to better survivability and serve as a prognostic biomarker for colorectal cancer (CRC). The RRM2B-overexpressing transfectant HCT-116/RRM2B or the corresponding vector control transfectant was implanted into NSG mouse to generate orthotopic xenograft mouse models. The lung and liver metastasis occurred in 60% of the HCT-116/vector mice (3 of 5 cases) but in none of the HCT-116/RRM2B mice (0 of 6 cases). The outcome studies were conducted on a training set with 103 CRC cases and were validated on a set with 220 consecutive CRC cases. All participants underwent surgery and periodically followed-up to determine survivability. Immunohistochemistry (IHC) was conducted on tissue arrays to determine the expression level of RRM2B. In the training set, the Kaplan-Meier and multivariate COX analysis revealed that the RRM2B is associated with better overall survival (OS) of CRC patients, especially in stage IV CRCs (Hazard ratio, HR=0.40; 95% CI 0.18-0.86). This result has been validated as HRs of RRM2B were 1.02 (95% CI 0.31-4.58) and 0.53(95% CI 0.29-1.01) for stage 0-II and stage III-IV, respectively. Multivariate analysis indicated that the adjusted HR of RRM2B was 0.48 (95% CI 0.26-0.91). Further analysis suggested that RRM2B significantly reduces the relative risk of death due to colon cancer (HR = 0.38; 95% CI 0.16-0.87) but not rectal cancer. Therefore, we conclude that RRM2B plays a critical role in suppressing invasiveness ability of cancer cells and it associates with a better prognosis for CRC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4183. doi:10.1158/1538-7445.AM2011-4183