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Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.pdf

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Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer

Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer Xiyong Liu1,*, Lily Lai2,*, Xiaochen Wang6,*, Lijun Xue1, Sofia Leora3, Jun Wu1, Shuya Hu1, Keqiang Zhang4, Mei-Ling Kuo1, Lun Zhou7, Hang Zhang7, Yafan Wang4, Yan Wang1, Bingsen Zhou1, Rebecca A Nelson5, Shu Zheng7, Suzhan Zhang7, Peiguo Chu2, and Yun Yen1,? 1 Department of Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA 91010 2 Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010 3 Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010 4 Translational Research Laboratory, City of Hope National Medical Center, Duarte, CA 91010 5 Division of Information Science, City of Hope National Medical Center, Duarte, CA 91010 6 Department of Surgical Oncology, 2nd Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang, China 310009 7 Cancer Institute, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang, China 310009 Abstract 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 r