Single‑center, retrospective, evaluator‑blinded, pilot and pivotal clinical trials: Assessing the mirCaP Kit (hsv2‑miR‑H9/hsa‑miR‑3659) as a diagnostic marker for prostate cancer in patients with PSA levels in the gray zone

Kim,Won Tae; Kim,Kyeong; Kang,Ho Won; Byun,Young Joon; Piao,Xuan-Mei; Kim,Yong-June; Lee,Sang Cheol; Yun,Seok Joong; Ha,Yun-Sok; Kim,Jiyeon; Kim,Isaac Yi

doi:10.3892/ol.2024.14770

Single‑center, retrospective, evaluator‑blinded, pilot and pivotal clinical trials: Assessing the mirCaP Kit (hsv2‑miR‑H9/hsa‑miR‑3659) as a diagnostic marker for prostate cancer in patients with PSA levels in the gray zone

Authors:
- Won Tae Kim
- Kyeong Kim
- Ho Won Kang
- Young Joon Byun
- Xuan-Mei Piao
- Yong-June Kim
- Sang Cheol Lee
- Seok Joong Yun
- Yun-Sok Ha
- Jiyeon Kim
- Isaac Yi Kim
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Affiliations: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea, Department of Urology, Chungbuk National University Hospital, Cheongju, Chungbuk 28644, Republic of Korea, Department of Urology, School of Medicine, Kyungpook National University, Daegu, North Gyeongsang 41404, Republic of Korea, Department of Urology, Yale School of Medicine, New Haven, CT 06510, USA
Published online on: October 23, 2024 https://doi.org/10.3892/ol.2024.14770
Article Number: 23

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Abstract

Prostate‑specific antigen (PSA) remains a key biomarker for the diagnosis and monitoring of prostate cancer (PCa). For patients within the ‘PSA gray zone’, the positive predictive value (PPV) of PSA for PCa detection by biopsy is estimated to be between 30 and 42%. In the present study, a single‑center, retrospective, evaluator‑blinded, pilot and pivotal clinical trial was performed to assess the clinical performance of the mirCaP kit (Urotech, Inc.), which measures the herpes simplex virus 2‑microRNA (miR)‑H9/hsa‑miR‑3659 ratio, with respect to helping physicians make appropriate decisions regarding further assessment of patients with PSA levels within this gray zone. For the patients in the initial clinical trial group who were in the PSA gray zone, the sensitivity, specificity, accuracy, PPV and negative predictive value (NPV) of the mirCaP kit were 94.29, 77.50, 85.33, 78.57 and 93.94%, respectively. For those in the pivotal clinical trial, these values were 94.50, 82.73, 87.90, 81.10 and 95.04%, respectively. These results suggest that the mirCaP kit may be an effective non‑invasive diagnostic marker for PCa in patients with PSA levels in the gray zone. Thus, the mirCaP kit is a promising tool that can help physicians make a decision regarding the need for prostate biopsy in these patients. Of note, the NPV of >90% indicates that the mirCaP kit could prevent unnecessary prostate biopsies in >90% of these cases.

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1	Siegel RL, Miller KD, Wagle NS and Jemal A: Cancer statistics, 2023. CA Cancer J Clin. 73:17–48. 2023. View Article : Google Scholar : PubMed/NCBI
2	Obirieze AC, Moten A, Allen D and Ahaghotu CA: African-American men with low-risk prostate cancer: Modern treatment and outcome trends. J Racial Ethn Health Disparities. 2:295–302. 2015. View Article : Google Scholar : PubMed/NCBI
3	Gann PH, Hennekens CH and Stampfer MJ: A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. JAMA. 273:289–294. 1995. View Article : Google Scholar : PubMed/NCBI
4	Shahab AA, Soebadi DM, Djatisoesanto W, Hardjowijoto S, Soetojo S and Hakim L: Prostate-specific antigen and prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer. Prostate Int. 1:23–30. 2013. View Article : Google Scholar : PubMed/NCBI
5	Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS and Redwine E: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 317:909–916. 1987. View Article : Google Scholar : PubMed/NCBI
6	Kobayashi M, Kijima T, Yashi M and Kamai T: Prostate-specific antigen kinetics contributes to decision making for biopsy referral: The predictive implication for PSA retest in patients with elevated PSA levels. Prostate Int. 11:27–33. 2023. View Article : Google Scholar : PubMed/NCBI
7	Wilson S and Crawford ED: Screening for prostate cancer: Current recommendations. Urol Clin North Am. 31:219–226. 2004. View Article : Google Scholar : PubMed/NCBI
8	Kim WT and Kim WJ: MicroRNAs in prostate cancer. Prostate Int. 1:3–9. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wang X, Liu S, Zhou Z, Yan H and Xiao J: A herpes simplex virus type 2-encoded microRNA promotes tumor cell metastasis by targeting suppressor of cytokine signaling 2 in lung cancer. Tumor Biol. 39:10104283177016332017.PubMed/NCBI
10	Choi J, Kwon SM, Moon SU, Yoon S, Shah M, Lee BG, Yang J, Park YN, Wang HJ and Woo HG: TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659. Liver Int. 41:2788–2800. 2021. View Article : Google Scholar : PubMed/NCBI
11	Yun SJ, Jeong P, Kang HW, Kim YH, Kim EA, Yan C, Choi YK, Kim D, Kim JM, Kim SK, et al: Urinary MicroRNAs of prostate cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p could be valuable diagnostic markers. Int Neurourol J. 19:74–84. 2015. View Article : Google Scholar : PubMed/NCBI
12	Byun YJ, Kang HW, Piao X, Zheng CM, Moon SK, Choi YH, Kim WT, Lee SC, Yun SJ and Kim WJ: Expression of hsv1-miR-H18 and hsv2-miR-H9 as a field defect marker for detecting prostate cancer. Prostate Int. 10:1–6. 2022. View Article : Google Scholar : PubMed/NCBI
13	Kang HW, Byun YJ, Kim K, Moon SM, Kim K, Piao XM, Zheng CM, Moon SK, Choi YH, Kim WT, et al: Urinary hsv2-miR-H9 to hsa-miR-3659 ratio is an effective marker for discriminating prostate cancer from benign prostate hyperplasia in patients within the prostate-specific antigen grey zone. Invest Clin Urol. 63:238–244. 2022. View Article : Google Scholar
14	Byun YJ, Piao XM, Jeong P, Kang HW, Seo SP, Moon SK, Lee JY, Choi YH, Lee HY, Kim WT, et al: Urinary microRNA-1913 to microRNA-3659 expression ratio as a non-invasive diagnostic biomarker for prostate cancer. Invest Clin Urol. 62:340–348. 2021. View Article : Google Scholar : PubMed/NCBI
15	Borley N and Feneley MR: Prostate cacner: Diagnosis and staging. Asian J Androl. 11:74–80. 2009. View Article : Google Scholar : PubMed/NCBI
16	Yun SJ, Jeong P, Kim W, Kim TH, Lee YS, Song PH, Choi YH, Kim IY, Moon SK and Kim WJ: Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. Int J Oncol. 41:1871–1878. 2012. View Article : Google Scholar : PubMed/NCBI
17	Kim WT, Jeong P, Yan C, Kim YH, Lee IS, Kang HW, Kim YJ, Lee SC, Kim SJ, Kim YT, et al: UBE2C cell-free RNA in urine can discriminate between bladder cancer and hematuria. Oncotarget. 7:58193–58202. 2016. View Article : Google Scholar : PubMed/NCBI
18	Piao XM, Jeong P, Kim YH, Byun YJ, Xu Y, Kang HW, Ha YS, Kim WT, Lee JY, Woo SH, et al: Urinary cell-free microRNA biomarker could discriminate bladder cancer from benign hematuria. Int J Cancer. 144:380–388. 2019. View Article : Google Scholar : PubMed/NCBI
19	Cho JS: Optimal prostate-specific antigen cutoff value in Korean. Korean J Urol Oncol. 5:1–5. 2007.(In Korean).
20	Oesterling JE, Jacobsen SJ and Cooner WH: The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. J Urol. 153:1160–1163. 1995. View Article : Google Scholar : PubMed/NCBI
21	Lee R, Localio AR, Armstrong K, Malkowicz SB and Schwartz JS; Free PSA Study Group, : A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology. 67:762–768. 2006. View Article : Google Scholar : PubMed/NCBI
22	Tang P, Du W, Xie K, Deng X, Fu J, Chen H and Yang W: Transition zone PSA density improves the prostate cancer detection rate both in PSA 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men. Urol Oncol. 31:744–748. 2013. View Article : Google Scholar : PubMed/NCBI
23	Carter HB, Ferrucci L, Kettermann A, Landis P, Wright EJ, Epstein JI, Trock BJ and Metter EJ: Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. J Natl Cancer Inst. 98:1521–1527. 2006. View Article : Google Scholar : PubMed/NCBI
24	Lepor A, Catalona WJ and Loeb S: The prostate health index: Its utility in prostate cancer detection. Urol Clin North Am. 43:1–6. 2016. View Article : Google Scholar : PubMed/NCBI
25	Parekh DJ, Punnen S, Sjoberg D, Asroff SW, Bailen JL, Cochran JS, Concepcion R, David RD, Deck KB, Dumbadze I, et al: A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 68:464–470. 2015. View Article : Google Scholar : PubMed/NCBI
26	Wei JT, Feng Z, Partin AW, Brown E, Thompson I, Sokoll L, Chan DW, Lotan Y, Kibel AS, Busby JE, et al: Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol. 32:4066–4072. 2014. View Article : Google Scholar : PubMed/NCBI
27	McKiernan J, Donovan MJ, O'Neill V, Bentink S, Noerholm M, Belzer S, Skog J, Kattan MW, Partin A, Andriole G, et al: A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol. 2:882–889. 2016. View Article : Google Scholar : PubMed/NCBI
28	Van Neste L, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, de Jong H, Hessels D, Smit FP, Melchers WJ, et al: Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol. 70:740–748. 2016. View Article : Google Scholar : PubMed/NCBI
29	de la Calle C, Patil D, Wei JT, Scherr DS, Sokoll L, Chan DW, Siddiqui J, Mosquera JM, Rubin MA and Sanda MG: Multicenter evaluation of the prostate health index to detect aggressive prostate cancer in biopsy Naïve men. J Urol. 194:65–72. 2015. View Article : Google Scholar : PubMed/NCBI
30	Davis JW, Nakanishi H, Kumar VS, Bhadkamkar VA, McCormack R, Fritsche HA, Handy B, Gornet T and Babaian RJ: Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: Initial results in early prostate cancer. J Urol. 179:2187–2191; discussion 2191. 2008. View Article : Google Scholar : PubMed/NCBI
31	Lau E, McCoy P, Reeves F, Chow K, Clarkson M, Kwan EM, Packwood K, Northen H, He M, Kingsbury Z, et al: Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression. Genome Med. 12:722020. View Article : Google Scholar : PubMed/NCBI
32	Cho H, Oh CK, Cha J, Chung JI, Byun SS, Hong SK, Chung JS and Han KH: Association of serum prostate-specific antigen (PSA) level and circulating tumor cell-based PSA mRNA in prostate cancer. Prostate Int. 10:14–20. 2022. View Article : Google Scholar : PubMed/NCBI
33	McKiernan J, Donovan MJ, Margolis E, Partin A, Carter B, Brown G, Torkler P, Noerholm M, Skog J, Shore N, et al: A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/ml at initial biopsy. Eur Urol. 74:731–738. 2018. View Article : Google Scholar : PubMed/NCBI
34	Manoj A, Ahmad MK, Prasad G, Kumar D, Mahdi A and Kumar M: Screening and validation of novel serum panel of microRNA in stratification of prostate cancer. Prostate Int. 11:150–158. 2023. View Article : Google Scholar : PubMed/NCBI
35	Glinge C, Clauss S, Boddum K, Jabbari R, Jabbari J, Risgaard B, Tomsits P, Hildebrand B, Kääb S, Wakili R, et al: Stability of circulating blood-based MicroRNAs-pre-analytic methodological considerations. PLoS One. 12:e01679692017. View Article : Google Scholar : PubMed/NCBI