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

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.

Sex

Male

Minimum age

45 Years

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.

• BACKGROUNDStrope SA, Andriole GL. Prostate cancer screening: current status and future perspectives. Nat Rev Urol. 2010 Sep;7(9):487-93. doi: 10.1038/nrurol.2010.120. PMID 20818326
• BACKGROUNDEpstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994 Feb 2;271(5):368-74. PMID 7506797
• BACKGROUNDPloussard 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. PMID 21601982
• BACKGROUNDMcKiernan 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. PMID 27032035
• BACKGROUNDDinh KT, Mahal BA, Ziehr DR, Muralidhar V, Chen YW, Viswanathan VB, Nezolosky MD, Beard CJ, Choueiri TK, Martin NE, Orio PF, Sweeney CJ, Trinh QD, Nguyen PL. Incidence and Predictors of Upgrading and Up Staging among 10,000 Contemporary Patients with Low Risk Prostate Cancer. J Urol. 2015 Aug;194(2):343-9. doi: 10.1016/j.juro.2015.02.015. Epub 2015 Feb 11. PMID 25681290
• BACKGROUNDChiu PK, Lai FM, Teoh JY, Lee WM, Yee CH, Chan ES, Hou SM, Ng CF. Prostate Health Index and %p2PSA Predict Aggressive Prostate Cancer Pathology in Chinese Patients Undergoing Radical Prostatectomy. Ann Surg Oncol. 2016 Aug;23(8):2707-14. doi: 10.1245/s10434-016-5183-6. Epub 2016 Mar 10. PMID 26965697
• BACKGROUNDSchiffer E. Biomarkers for prostate cancer. World J Urol. 2007 Dec;25(6):557-62. doi: 10.1007/s00345-007-0203-6. Epub 2007 Aug 10.