Identification and Validation of a Five MicroRNA Signature Predictive of Prostate Cancer Recurrence and Metastasis: A Cohort Study

被引：31

作者：

Nam, Robert K. ^{[1
]}

Amemiya, Yutaka ^{[2
]}

Benatar, Tania ^{[2
]}

Wallis, Christopher J. D. ^{[1
]}

Stojcic-Bendavid, Jessica ^{[1
]}

Bacopulos, Stephanie ^{[2
]}

Sherman, Christopher ^{[3
]}

Sugar, Linda ^{[3
]}

Naeim, Magda ^{[3
]}

Yang, Wenyi ^{[2
]}

Zhang, Aiguo ^{[2
]}

Klotz, Laurence H. ^{[1
]}

Narod, Steven A. ^{[4
]}

Seth, Arun ^{[2
]}

机构：

[1] Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Div Urol, Toronto, ON M4N 3M5, Canada

[2] Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Dept Anat Pathol,Platform Biol Sci, Toronto, ON M4N 3M5, Canada

[3] Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Dept Lab Med & Pathobiol, Toronto, ON M4N 3M5, Canada

[4] Univ Toronto, Dept Publ Hlth Sci, Toronto, ON M5G 1N8, Canada

来源：

JOURNAL OF CANCER | 2015年 / 6卷 / 11期

关键词：

MicroRNA; Prostatic neoplasms; Prostatectomy; High-throughput nucleotide sequencing; RADICAL PROSTATECTOMY; CELL-PROLIFERATION; COLORECTAL-CANCER; GASTRIC-CANCER; EXPRESSION; MIR-301A; RADIOTHERAPY; CARCINOMA; SURVIVAL; INVASION;

D O I：

10.7150/jca.13397

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: MicroRNA (miRNA) have been shown to be important in regulating gene expression in prostate cancer. We used next generation miRNA sequencing to conduct a whole miRNome analysis to identify miRNAs associated with prostate cancer metastasis. Methods: We conducted discovery and validation analyses of miRNAs among a total of 546 men who underwent surgery for prostate cancer using the development of metastasis as an endpoint. Genome wide analysis was conducted among the discovery group (n=31) to identify new miRNAs associated with prostate cancer metastasis. Selected miRNAs were then analyzed using qPCR on prostatectomy specimens from an independent cohort (n=515) to determine whether their expression could predict the development of metastasis after surgery. To examine the biology underlying these associations, we created prostate cancer cell lines which overexpressed miR-301a for in vitro and in vivo functional assays. Results: We identified 33 miRNAs associated with prostate cancer metastasis and selected a panel comprising miRs-301a, 652, 454, 223 and 139 which strongly predicted metastasis (AUC=95.3%, 95% C.I.: 84%-99%). Among the validation cohort, the 15-year metastasis-free survival was 77.5% (95% C.I.: 63.9%-86.4%) for patients with a high miRNA panel score and 98.8% (95% C.I.: 94.9%-99.7%, p<0.0001 for difference) for those with a low score. After adjusting for grade, stage, and PSA, the hazard ratio for metastasis was 4.3 (95% C.I.: 1.7-11.1, p=0.002) for patients with a high miRNA panel score, compared to those with a low score. Prostate cancer cell lines overexpressing miR-301a had in significantly higher tumor growth and metastasis in a xenograft mouse model. Conclusions: A panel of miRNAs is associated with prostate cancer metastasis. These could be used as potential new prognostic factors in the surgical management of prostate cancer.

引用

页码：1160 / 1171

页数：12