title: Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.
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.
authors.affiliation: Department of Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.forename: Lily
authors.initials: L
authors.lastname: Lai
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Xue
authors.forename: Sofia
authors.initials: S
authors.lastname: Leora
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Shuya
authors.initials: S
authors.lastname: Hu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Kuo
authors.forename: Lun
authors.initials: L
authors.lastname: Zhou
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Yafan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Nelson
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Suzhan
authors.initials: S
authors.lastname: Zhang
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012264:Ribonucleotide Reductases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015996:Survival Rate; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases