Circulating microRNAs predict biochemical recurrence in prostate cancer patients

Selth, Luke A.; Townley, Scott L.; Bert, Andrew G.; Stricker, Phillip D.; Sutherland, Peter; Horvath, Lisa G.; Goodall, Gregory J.; Butler, Lisa M.; Tilley, Wayne D.

doi:10.1038/bjc.2013.369

Cited by 119 publications

(105 citation statements)

References 48 publications

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“…Among the 130 miRNAs that showed high expression in our present study, 18 have already been linked to PCa relapse (11)(12)(13)(27)(28)(29)(30). Our results are in agreement with earlier reports that showed that miR-26b, miR-30a-3p, and miR-26a correlate with biochemical failure (12 ).…”

Section: Discussionsupporting

confidence: 93%

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

et al. 2013

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PURPOSE Prostate-specific antigen testing has led to overtreatment of prostate cancer (PCa). Only a small subset of PCa patients will have an aggressive disease that requires intensive therapy, and there is currently no biomarker to predict disease aggressiveness at the time of surgery. MicroRNAs (miRNAs) are reported to be involved in PCa pathogenesis. METHODS This study involved 105 participants. For the discovery phase, prostatectomy samples were dichotomized to high-risk (n = 27, biochemical failure <36 months after prostatectomy) and low-risk groups (n = 14, ≥36 months without biochemical failure). Expression of 754 mature miRNAs was compared between the 2 groups. Linear regression models were built to accurately predict biochemical failure risk. miRNA mimics were transfected into PCa model cell lines to test effects on proliferation and to deduce responding signaling pathways. RESULTS We identified 25 differentially expressed miRNAs between the biochemical failure risk groups. Based on the expression of 2–3 miRNAs, 3 logistic regression models were developed, each with a high positive predictive value. Candidate miRNAs and the best-performing model were also verified on an independent PCa set. miRNA-152, featured in the models, was further investigated by using cell line models and was shown to affect cell proliferation. Predicted interaction between miR-152 and (mRNA)ERBB3 (erythroblastic leukemia viral oncogene homolog 3) was experimentally validated in vitro. CONCLUSIONS miRNAs can help to predict biochemical failure risk at the time of prostatectomy.

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Section: Discussionsupporting

confidence: 93%

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

et al. 2013

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“…Patients with lower miR-141 were more likely to have systemic lupus erythematosus (14 ). In cancers, higher concentrations of miR-141 in resected colorectal cancer patients were found to be associated with long-term and disease-free survival (15 ), on the one hand, but on the other, and seemingly more consistently, with poor outcomes including biochemical recurrence (16 ), increased metastasis (17 ) in prostate cancer, or poor prognosis in prostate cancer (18 ), hepatocellular carcinoma (19 ), and colon cancer (20 ). Results obtained in an identification cohort supported association of miR-141 with bladder cancer; however, this was not confirmed in a validation cohort (21 ).…”

Section: Diagnostic Specificity and Reproducibility Multiple Associatmentioning

confidence: 98%

Circulating MicroRNA Biomarker Studies: Pitfalls and Potential Solutions

2015

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BACKGROUND Circulating microRNAs have been proposed as disease biomarkers that may aid in risk assessment, diagnosis, prognosis, and monitoring of treatment response. The perceived opportunity has loomed particularly large in neoplastic disease, where alterations in cancer cells are thought to be reflected in the extracellular space as affected cells release upregulated miRNAs or fail to release apparently downregulated species. Despite the promise of miRNA biomarkers, evaluation of the diagnostic specificity and reproducibility of reported markers suggests that realizing this promise remains a work in progress. CONTENTS This review examines issues of diagnostic specificity and reproducibility that have afflicted circulating miRNA studies. Surveying the breast cancer literature as an example, few miRNAs are reported consistently. Furthermore, it is posited that the assumptions underlying models of direct contributions of diseased tissue to biofluid miRNA profiles may not hold. Suggestions for improving diagnostic specificity and reliability are provided. SUMMARY To maximize the likelihood of return on investment as miRNAs continue to be evaluated as specific and clinically useful markers, a focus is needed on miRNAs found in specific carriers, such as extracellular vesicles. Alternative sampling techniques should be developed, and nonblood biofluids should be considered. Careful optimization and standardization of preanalytical and analytical methods is needed to ensure that future results, positive or negative, are reliable.

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“…[39][40][41][42][43] miRNAs hold considerable promise to be exploited as highly accurate and functional prognostic serum markers of CaP stages and drug responses. 27,[44][45][46][47][48][49][50][51][52][53][54] They can encapsulate events within the tumor microenvironment, thereby overcoming the limitations of sampling error at biopsy. In parallel, it has become apparent that changes in miRNA regulation in tumors is translated to altered serum expression patterns and, therefore, offers an important diagnostic and prognostic therapeutic window.…”

Section: Introductionmentioning

confidence: 99%

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

et al. 2015

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The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1a,25(OH) 2 D 3 . Across all models, 111 miRNAs were significantly modulated by 1a,25(OH) 2 D 3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1a,25 (OH) 2 D 3 -regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.

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Circulating microRNAs predict biochemical recurrence in prostate cancer patients

Cited by 119 publications

References 48 publications

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

Circulating MicroRNA Biomarker Studies: Pitfalls and Potential Solutions

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

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