Abstract
Purpose: To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). Materials and methods: A retrospective outcome study was conducted on 164 eligible PCa samples from the City of Hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays, Ras/Raf, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. Results: Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P-, capsule-, and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was proportional to RRM2 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. Conclusion: RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients with low-risk PCa.
| Original language | English |
|---|---|
| Journal | Urologic Oncology: Seminars and Original Investigations |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2014 |
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Keywords
- Biochemical recurrence
- Gleason score
- Prognostic biomarker
- Prostate cancer
- Ribonucleotide reductase M2
ASJC Scopus subject areas
- Oncology
- Urology
Cite this
The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers. / Huang, Yasheng; Liu, Xiyong; Wang, Yuan Hung; Yeh, Shauh Der; Chen, Chi Long; Nelson, Rebecca A.; Chu, Peiguo; Wilson, Timothy; Yen, Yun.
In: Urologic Oncology: Seminars and Original Investigations, Vol. 32, No. 1, 01.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers
AU - Huang, Yasheng
AU - Liu, Xiyong
AU - Wang, Yuan Hung
AU - Yeh, Shauh Der
AU - Chen, Chi Long
AU - Nelson, Rebecca A.
AU - Chu, Peiguo
AU - Wilson, Timothy
AU - Yen, Yun
PY - 2014/1
Y1 - 2014/1
N2 - Purpose: To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). Materials and methods: A retrospective outcome study was conducted on 164 eligible PCa samples from the City of Hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays, Ras/Raf, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. Results: Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P-, capsule-, and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was proportional to RRM2 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. Conclusion: RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients with low-risk PCa.
AB - Purpose: To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). Materials and methods: A retrospective outcome study was conducted on 164 eligible PCa samples from the City of Hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays, Ras/Raf, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. Results: Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P-, capsule-, and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was proportional to RRM2 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. Conclusion: RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients with low-risk PCa.
KW - Biochemical recurrence
KW - Gleason score
KW - Prognostic biomarker
KW - Prostate cancer
KW - Ribonucleotide reductase M2
UR - http://www.scopus.com/inward/record.url?scp=84890673363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890673363&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2013.08.002
DO - 10.1016/j.urolonc.2013.08.002
M3 - Article
VL - 32
JO - Urologic Oncology
JF - Urologic Oncology
SN - 1078-1439
IS - 1
ER -