Journal
PROSTATE
Volume 78, Issue 2, Pages 121-127Publisher
WILEY
DOI: 10.1002/pros.23452
Keywords
circulating biomarker; miR-141; miR-200; miR-375; microRNA; prostate cancer
Categories
Funding
- Prostate Cancer Foundation
- NIH Clinical Center [CA142559, CA35281, CA35090, CA37981, CA45807, CA, CA180801, CA180818 CA180819, CA180828, CA46368, CA180835, CA35421, CA35431, CA58416, CA63848, CA63844, CA12644, CA110]
- National Institutes of Health [CA180801, 5TR01 R01DK085714]
- National Cancer Institute [CA097186, CA32102, CA38926]
- NATIONAL CANCER INSTITUTE [U10CA037981, P50CA097186, U10CA058416, U10CA142559, U10CA180834, U10CA063848, U10CA035431, U10CA046282, U10CA180828, U10CA180819, U10CA035090, U10CA035421, U10CA035281, U10CA180801, U10CA045808, U10CA046368, U10CA180888, U10CA035178, U10CA012644, U10CA045807, U10CA067575, U10CA180818, U10CA180830, U10CA180846, U10CA011083, U10CA180835, U10CA063844, UG1CA233178] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK085714] Funding Source: NIH RePORTER
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BackgroundPrevious studies suggest circulating, blood-based microRNAs (miRNAs) may serve as minimally invasive prostate cancer biomarkers, however there is limited data from prospective clinical trials. Here, we explore the role of candidate plasma miRNAs as potential biomarkers in the SWOG 0925 randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone-sensitive prostate cancer. MethodsCorrelative biospecimens, including circulating tumor cells (CTCs) and plasma for miRNA analysis, were collected at baseline and after 12 weeks on treatment from 50 patients enrolled on SWOG 0925. Circulating microRNAs were quantified using real-time RT-PCR microRNA array that allowed specific analysis of previously identified candidate miRNAs (miR-141, miR-200a, miR-200b, miR-210, and miR-375) as well as discovery analysis to identify new candidate miRNAs. MiRNA levels were correlated to previously reported CTC counts using CellSearch (R) (Veridex) and with the primary study outcome of 28-week PSA response (0.2, 0.2 to 4.0, or >4.0ng/mL), previously shown to correlate with overall survival. ResultsWe observed a correlation between baseline circulating miR-141, miR-200a, and miR-375 levels with baseline CTCs. Baseline miR-375 levels were associated with 28-week PSA response (0.2, 0.2 to 4.0, or >4.0ng/mL, P=0.007). Using ROC curve analysis, there was no significant difference between baseline miR-375 and baseline CTC in predicting 28-week PSA response (0.2 vs >0.2ng/mL). To discover novel candidate miRNAs, we analyzed 365 miRNAs for association with the 28-week PSA response endpoint and identified new candidate miRNAs along with the existing candidates miR-375 and miR-200b (P=0.0012, P=0.0046, respectively. ConclusionsBaseline plasma miR-141, miR-200a, and miR-375 levels are associated with baseline CTC count. Baseline miR-375 was also associated with the trial endpoint of 28-week PSA response. Our results provide evidence that circulating miRNA biomarkers may have value as prognostic biomarkers and warrant further study in larger prospective clinical trials.
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