Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer

Xiyong Liu, Lily Lai, Xiaochen Wang, Lijun Xue, Sofia Leora, Jun Wu, Shuya Hu, Keqiang Zhang, Mei Ling Kuo, Lun Zhou, Hang Zhang, Yafan Wang, Yan Wang, Bingsen Zhou, Rebecca A. Nelson, Shu Zheng, Suzhan Zhang, Peiguo Chu, Yun Yen

Research output: Contribution to journalArticle

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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 are correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in nonmetastatic 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 carry out immunohistochemistry 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 (HR = 0.40; 95% CI = 0.18-0.86, P = 0.016). In the validation set, RRM2B was negatively related to tumor invasion (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). Furthermore, 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 and IV tumors rather than earlier stage I and 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.

Original languageEnglish
Pages (from-to)3202-3213
Number of pages12
JournalCancer Research
Volume71
Issue number9
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

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Ribonucleotide Reductases
Colorectal Neoplasms
Survival
Neoplasms
Multivariate Analysis
Neoplasm Metastasis
Heterografts
Fluorescence
Lymph Nodes
Immunohistochemistry
Outcome Assessment (Health Care)
Lung
Antibodies
Liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer. / Liu, Xiyong; Lai, Lily; Wang, Xiaochen; Xue, Lijun; Leora, Sofia; Wu, Jun; Hu, Shuya; Zhang, Keqiang; Kuo, Mei Ling; Zhou, Lun; Zhang, Hang; Wang, Yafan; Wang, Yan; Zhou, Bingsen; Nelson, Rebecca A.; Zheng, Shu; Zhang, Suzhan; Chu, Peiguo; Yen, Yun.

In: Cancer Research, Vol. 71, No. 9, 01.05.2011, p. 3202-3213.

Research output: Contribution to journalArticle

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 2011, 'Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer', Cancer Research, vol. 71, no. 9, pp. 3202-3213. https://doi.org/10.1158/0008-5472.CAN-11-0054
Liu, Xiyong ; Lai, Lily ; Wang, Xiaochen ; Xue, Lijun ; Leora, Sofia ; Wu, Jun ; Hu, Shuya ; Zhang, Keqiang ; Kuo, Mei Ling ; Zhou, Lun ; Zhang, Hang ; Wang, Yafan ; Wang, Yan ; Zhou, Bingsen ; Nelson, Rebecca A. ; Zheng, Shu ; Zhang, Suzhan ; Chu, Peiguo ; Yen, Yun. / Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer. In: Cancer Research. 2011 ; Vol. 71, No. 9. pp. 3202-3213.
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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 are correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in nonmetastatic 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 carry out immunohistochemistry 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 (HR = 0.40; 95{\%} CI = 0.18-0.86, P = 0.016). In the validation set, RRM2B was negatively related to tumor invasion (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). Furthermore, 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 and IV tumors rather than earlier stage I and 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.",
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AU - Wu, Jun

AU - Hu, Shuya

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AU - Wang, Yafan

AU - Wang, Yan

AU - Zhou, Bingsen

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