Phase 2 Study of Circulating MicroRNA Biomarkers in Castration-resistant Prostate Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 Mar 10

PMID 28278515

Citations 33

Authors

Hui-Ming Lin

Kate L Mahon

Calan Spielman

Howard Gurney

Girish Mallesara

Martin R Stockler

Patricia Bastick

Karen Briscoe

Gavin Marx

Alexander Swarbrick

Lisa G Horvath

Affiliations

Soon will be listed here.

Abstract

Background: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.

Methods: Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients.

Results: The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors.

Conclusions: The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.

Citing Articles

Relationship between circulating miRNA-222-3p and miRNA-136-5p and the efficacy of docetaxel chemotherapy in metastatic castration-resistant prostate cancer patients.

Yuan S, Bi X, Shayiti F, Niu Y, Chen P BMC Urol. 2024; 24(1):275.

PMID: 39709424 PMC: 11662419. DOI: 10.1186/s12894-024-01666-7.

Plasma microRNA Signature as Companion Diagnostic for Abiraterone Acetate Treatment in Metastatic Castration-Resistant Prostate Cancer: A Pilot Study.

Detassis S, Precazzini F, Grasso M, Del Vescovo V, Maines F, Caffo O Int J Mol Sci. 2024; 25(11).

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Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review.

Maekawa S, Takata R, Obara W Cancers (Basel). 2024; 16(3).

PMID: 38339274 PMC: 10854717. DOI: 10.3390/cancers16030523.

miRNA Expression Patterns in Early- and Late-Stage Prostate Cancer Patients: High-Throughput Analysis.

Gilyazova I, Ivanova E, Gupta H, Mustafin A, Ishemgulov R, Izmailov A Biomedicines. 2023; 11(11).

PMID: 38002073 PMC: 10669269. DOI: 10.3390/biomedicines11113073.

Nanoribbon Biosensor-Based Detection of microRNA Markers of Prostate Cancer.

Ivanov Y, Malsagova K, Goldaeva K, Kapustina S, Pleshakova T, Popov V Sensors (Basel). 2023; 23(17).

PMID: 37687982 PMC: 10490786. DOI: 10.3390/s23177527.

References

Cheng H, Mitchell P, Kroh E, Dowell A, Chery L, Siddiqui J . Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One. 2013; 8(7):e69239. PMC: 3728349. DOI: 10.1371/journal.pone.0069239. View

Korpal M, Ell B, Buffa F, Ibrahim T, Blanco M, Celia-Terrassa T . Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011; 17(9):1101-8. PMC: 3169707. DOI: 10.1038/nm.2401. View

Thieu W, Tilki D, de Vere White R, Evans C . The role of microRNA in castration-resistant prostate cancer. Urol Oncol. 2014; 32(5):517-523. PMC: 4570565. DOI: 10.1016/j.urolonc.2013.11.004. View

Taganov K, Boldin M, Chang K, Baltimore D . NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006; 103(33):12481-6. PMC: 1567904. DOI: 10.1073/pnas.0605298103. View

Halabi S, Lin C, Kelly W, Fizazi K, Moul J, Kaplan E . Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014; 32(7):671-7. PMC: 3927736. DOI: 10.1200/JCO.2013.52.3696. View

Hart M, Nolte E, Wach S, Szczyrba J, Taubert H, Rau T . Comparative microRNA profiling of prostate carcinomas with increasing tumor stage by deep sequencing. Mol Cancer Res. 2013; 12(2):250-63. DOI: 10.1158/1541-7786.MCR-13-0230. View

Tannock I, de Wit R, Berry W, Horti J, Pluzanska A, Chi K . Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004; 351(15):1502-12. DOI: 10.1056/NEJMoa040720. View

Qu W, Ding S, Cao G, Wang S, Zheng X, Li G . miR-132 mediates a metabolic shift in prostate cancer cells by targeting Glut1. FEBS Open Bio. 2016; 6(7):735-41. PMC: 4932453. DOI: 10.1002/2211-5463.12086. View

Ferraldeschi R, Welti J, Luo J, Attard G, de Bono J . Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects. Oncogene. 2014; 34(14):1745-57. PMC: 4333106. DOI: 10.1038/onc.2014.115. View

10.

Zhang H, Yang L, Zhu Y, Yao X, Zhang S, Dai B . Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2010; 71(3):326-31. DOI: 10.1002/pros.21246. View

11.

Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne R . miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol. 2010; 12(5):513-9. DOI: 10.1038/ncb2054. View

12.

Sita-Lumsden A, Dart D, Waxman J, Bevan C . Circulating microRNAs as potential new biomarkers for prostate cancer. Br J Cancer. 2013; 108(10):1925-30. PMC: 3670496. DOI: 10.1038/bjc.2013.192. View

13.

Scher H, Halabi S, Tannock I, Morris M, Sternberg C, Carducci M . Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008; 26(7):1148-59. PMC: 4010133. DOI: 10.1200/JCO.2007.12.4487. View

14.

Gonzales J, Fink L, Goodman Jr O, Symanowski J, Vogelzang N, Ward D . Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer. Clin Genitourin Cancer. 2011; 9(1):39-45. DOI: 10.1016/j.clgc.2011.05.008. View

15.

Tian H, Hou L, Xiong Y, Huang J, Zhang W, Pan Y . miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells. Am J Transl Res. 2016; 8(3):1492-501. PMC: 4859634. View

16.

Turchinovich A, Samatov T, Tonevitsky A, Burwinkel B . Circulating miRNAs: cell-cell communication function?. Front Genet. 2013; 4:119. PMC: 3695387. DOI: 10.3389/fgene.2013.00119. View

17.

Janssen H, Reesink H, Lawitz E, Zeuzem S, Rodriguez-Torres M, Patel K . Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368(18):1685-94. DOI: 10.1056/NEJMoa1209026. View

18.

Bishr M, Saad F . Overview of the latest treatments for castration-resistant prostate cancer. Nat Rev Urol. 2013; 10(9):522-8. DOI: 10.1038/nrurol.2013.137. View

19.

Petrylak D, Tangen C, Hussain M, Lara Jr P, Jones J, Taplin M . Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004; 351(15):1513-20. DOI: 10.1056/NEJMoa041318. View

20.

Fujita Y, Yoshioka Y, Ochiya T . Extracellular vesicle transfer of cancer pathogenic components. Cancer Sci. 2016; 107(4):385-90. PMC: 4832849. DOI: 10.1111/cas.12896. View