Exosomal microRNA in Predicting the Aggressiveness of Prostate Cancer in Chinese Patients

Prostate Cancer Clinical Trial

Official title:

To Investigate the Diagnostic Accuracy of Exosomal microRNA in Predicting the Aggressiveness of Prostate Cancer in Chinese Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03911999
• Other study ID #: CRE-2018.063
• Status: Completed
• Start date: May 3, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2021
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The prostate gland is a clinically important male accessory sex gland and vital for its production of semen. Prostate cancer (PCa) is now ranked 3th in annual incidence of male cancer and ranked 5th for cancer-related death in men in Hong Kong which accounts for about 10.9 deaths per 100,000 persons. Its incidence is rising rapidly, almost tripled in the past 10 years. Fortunately, with the improvement in awareness of the disease and also increasing use of serum prostate specific antigen for early case identification, many patients are diagnosed at an earlier stage. However, unlike other malignancy, PCa is characterized by its slow progression nature. Therefore, some patients with low grade low volume disease might never suffered from PCa related complications or mortality. As a result, recent year, there is an increase use a more conservative approach, active surveillance (AS), for management of early prostate cancer. The principle of AS is selecting patients with low risk of disease and offered them regular monitoring, instead of radical local therapy, unless patient's cancer was noticed to progressing. By using this approach, patients might avoid possible complications related to treatment. Currently, people could use some clinical parameters, imaging and repeated prostate biopsy to assess and monitor the aggressiveness/ progression of PCa. However, these parameters suffered from defects, such as low correlation to the final PCa pathology or not readily repeatable for patients. Therefore, there is a need to identify more easy, safe and repeatable monitoring of the aggressiveness of prostate cancer.

Exosome is genetic materials secreted by cells and could be measured in various body fluid. There are some studies suggested it is a potential marker for PCa diagnosis and monitoring. The aim of this study is to investigate the relationship of urinary exosome and the aggressiveness of prostate cancer.

Description:

Prostate cancer (PCa) is the third most common male cancer in Hong Kong. While the use of serum PSA has greatly improved the proportion of patients diagnosed at localized /early stage, there are also problems of overdiagnosis and overtreatment. Unfortunately, there was still no ideal markers that could help to predict the aggressiveness of PCa, especially in Chinese population. Exosome is an important media for cell-cell interaction. The content of exomsomes, including microRNAs, are believed to have important roles in PCa development and progression, and might also serve as potential markers in PCa management. Therefore, investigators would like to explore the role of exosomal microRNA in the prediction of tumour aggressiveness in local Chinese PCa patients. This is a prospective study divided into two parts. Subjects will be recruited consecutively from two hospitals.

In Part I of the study (Candidate exosomal microRNA discovery and selection), a total of 60 patients from three groups (non-cancer, pathologically insignificant cancer and significant cancer patients) will be recruited. First portion of urine will be collected from them. For Group 2&3 patients, they are patients with clinically localized prostate cancer and planned for radical prostatectomy, urine will be collected before surgery for these two groups. Exosomal RNA will be extracted from urine and microRNAs expression profiles will be determined by next-generation sequencing. Candidate exosomal microRNAs that could differentiate pathological insignificant and significant PCa will be identified for Part II study.

In Part II study (Candidate exosomal microRNAs validation), 180 patients with localized prostate cancer, planned for radical prostatectomy will be recruited. Urine will be again collected before surgery and the level of candidate exosomal microRNAs for each patient will be assessed. The diagnostic accuracy of these candidate exosomal microRNAs on predicting pathological insignificant cancer and also correlation with the final pathology will be assessed.

The primary tasks for Part I study is the identification of potential exosomal microRNAs that could differentiate pathologically insignificant and significant PCa.

The primary task for Part II study is the validation of the ability of those candidate exosomal microRNAs in differentiating pathological insignificant and significant PCa.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 31, 2020
• Est. primary completion date: November 15, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

1. For non prostate cancer group

• Male subject with age 45 or above

• No clinical evidence of PCa, serum PSA <4 ng/dl and normal digital rectal examination.

2. For prostate cancer group

• Male subject with age 45 or above

• Clinically diagnosed to have localized PCa and planned for radical prostatectomy

• No prior systemic therapy for PCa used, including hormonal or chemotherapy.

Exclusion Criteria:

• History of medications usage that can affect serum PSA levels within 6 months of study enrolment.

• History of active urinary tract infection within 1 month of study enrolment.

• History of invasive prostate / bladder treatments within 6 months of study enrolment.

• History of concurrent renal/bladder cancer within 6 months of study enrolment.

Related Conditions & MeSH terms

• Aggression
• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (18)

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Leung YK, Chan QK, Ng CF, Ma FM, Tse HM, To KF, Maranchie J, Ho SM, Lau KM. Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer. PLoS One. 2014 May 16;9(5):e98037. doi: 10.1371/journal.pone.0098037. eCollection 2014. Erratum in: PLoS One. 2019 Mar 18;14(3):e0214184. — View Citation

McKiernan J, Donovan MJ, O'Neill V, Bentink S, Noerholm M, Belzer S, Skog J, Kattan MW, Partin A, Andriole G, Brown G, Wei JT, Thompson IM Jr, Carroll P. A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncol. 2016 Jul 1;2(7):882-9. doi: 10.1001/jamaoncol.2016.0097. — View Citation

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Ploussard G, Epstein JI, Montironi R, Carroll PR, Wirth M, Grimm MO, Bjartell AS, Montorsi F, Freedland SJ, Erbersdobler A, van der Kwast TH. The contemporary concept of significant versus insignificant prostate cancer. Eur Urol. 2011 Aug;60(2):291-303. doi: 10.1016/j.eururo.2011.05.006. Epub 2011 May 17. Review. — View Citation

Ren S, Peng Z, Mao JH, Yu Y, Yin C, Gao X, Cui Z, Zhang J, Yi K, Xu W, Chen C, Wang F, Guo X, Lu J, Yang J, Wei M, Tian Z, Guan Y, Tang L, Xu C, Wang L, Gao X, Tian W, Wang J, Yang H, Wang J, Sun Y. RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res. 2012 May;22(5):806-21. doi: 10.1038/cr.2012.30. Epub 2012 Feb 21. — View Citation

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Wang G, Chan ES, Kwan BC, Li PK, Yip SK, Szeto CC, Ng CF. Expression of microRNAs in the urine of patients with bladder cancer. Clin Genitourin Cancer. 2012 Jun;10(2):106-13. doi: 10.1016/j.clgc.2012.01.001. Epub 2012 Mar 3. — View Citation

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Zhang DZ, Lau KM, Chan ES, Wang G, Szeto CC, Wong K, Choy RK, Ng CF. Cell-free urinary microRNA-99a and microRNA-125b are diagnostic markers for the non-invasive screening of bladder cancer. PLoS One. 2014 Jul 11;9(7):e100793. doi: 10.1371/journal.pone.0100793. eCollection 2014. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the differences in microRNA expression between non-prostate cancer subjects, pathologically insignificant and significant prostate cancer patients.	Urine will be collected prior to surgery. The urine sample will then be handled immediately for exosomal RNA extraction (refer to specific methodology). The extracted exosomal RNA would then be stored for next generation sequencing (NGS). Results of the 3 groups will then be compared, with reference to literatures findings. Candidate microRNAs that can differentiate between pathologically significant and insignificant cancer will be selected for Part II study.	Baseline, one-time point
Primary	To assess the accuracy of selected microRNAs for the differentiation of patients with pathologically insignificant and significant prostate cancer after radical prostatectomy	Urine will be collected prior to surgery. The urine sample will then be handled immediately for exosomal RNA extraction (refer to specific methodology). The extracted exosomal RNA would then be stored for next generation sequencing (NGS). Results of the 3 groups will then be compared, with reference to literatures findings. Candidate microRNAs that can differentiate betten pathologically significant and insignificant cancer will be selected for Part II study.The preoperative patients and disease parameters, including age, clinical staging, serum PSA level, prostatic biopsy results, MRI findings, together with the prostatectomy pathology will be collected for subsequent data analysis.	Baseline, one-time point