Dataset Information

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.

SUBMITTER: Liu X

PROVIDER: S-EPMC3085570 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Xiyong X Lai Lily L Wang Xiaochen X Xue Lijun L Leora Sofia S Wu Jun J Hu Shuya S Zhang Keqiang K Kuo Mei-Ling ML Zhou Lun L Zhang Hang H Wang Yafan Y Wang Yan Y Zhou Bingsen B Nelson Rebecca A RA Zheng Shu S Zhang Suzhan S Chu Peiguo P Yen Yun Y

Cancer research 20110317 9

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 ...[more]

PMID: 21415168

Similar Datasets

Project description:Although there are molecularly distinct subtypes of prostate cancer, no molecular classification system is used clinically. The ribonucleotide reductase small subunit M2 (RRM2) gene plays an oncogenic role in many cancers. Our previous study elucidated comprehensive molecular mechanisms of RRM2 in prostate cancer (PC). Given the potent functions of RRM2, we set out to determine whether the RRM2 signature can be used to identify aggressive subtypes of PC. We applied gene ontology and pathway analysis in RNA-seq datasets from PC cells overexpressing RRM2. We refined the RRM2 signature by integrating it with two molecular classification systems (PCS and PAM50 subtypes) that define aggressive PC subtypes (PCS1 and luminal B) and correlated signatures with clinical outcomes in six published cohorts comprising 4000 cases of PC. Increased expression of genes in the RRM2 signature was significantly correlated with recurrence, high Gleason score, and lethality of PC. Patients with high RRM2 levels showed higher PCS1 score, suggesting the aggressive PC feature. Consistently, RRM2-regulated genes were highly enriched in the PCS1 signature from multiple PC cohorts. A simplified RRM2 signature (12 genes) was identified by intersecting the RRM2 signature, PCS1 signature, and the PAM50 classifier. Intriguingly, inhibition of RRM2 specifically targets PCS1 and luminal B genes. Furthermore, 11 genes in the RRM2 signature were correlated with enzalutamide resistance by using a single-cell RNA-seq dataset from PC circulating tumor cells. Finally, high expression of RRM2 was associated with an immunosuppressive tumor-immune microenvironment in both primary prostate cancer and metastatic prostate cancer using CIBERSORT analysis and LM22, a validated leukocyte gene signature matrix. These data demonstrate that RRM2 is a driver of aggressive prostate cancer subtypes and contributes to immune escape, suggesting that RRM2 inhibition may be of clinical benefit for patients with PC.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets