Introduction: Prostate cancer (PCa) is the second cause of cancer death in men worldwide. Current treatments are not effective enough, as there is a challenge in the clinical management of PCa is the inefficiency of present methods for early detection of PCa, such as quantitative serum PSA testing and Digital Rectal Examination DRE. Quantitative determination of PSA is inappropriate in indolent forms of PCa, does not have sufficient sensitivity and specificity to identify and classify cancers at lower stages, and usually does not eliminate the need for biopsy or repeat of the biopsy, which causes the patient anxiety. Typically, 70% of PCa cases did not diagnose at initial biopsy because of false-negative or tumor heterogeneity. DRE also has side effects such as infection with antibiotic-resistant pathogenic bacteria and the risk of rectal damage and rupture.
Recently exosomes have been used in the diagnosis of solid tumors and targeted drug delivery. Exosomes contain proteins, lipids, DNAs, mRNAs, and non-coding RNAs found in body fluids such as serum, plasma, saliva, cerebrospinal fluid, milk, semen, and urine. Also, the unique properties of exosomes like non-invasiveness, stability, biocompatibility, permeability, low toxicity, small size(50-150 nm), low immunogenicity, and their significant amount in body fluids make them suitable carriers of potential biomarkers for prostate cancer diagnosis. Examining the expression changes of non-coding RNAs, especially MicroRNAs, due to their high sensitivity and specificity in urinary exosomes (ExomiRs) between PCa patients and the control group can be a prominent step in non-invasive and early detection of PCa.
Methods: Search for the keywords Biomarker, Prostate cancer, Diagnosis, MicroRNA, Urinary exosomes, and Non-invasive in PubMed and Google scholar databases had more than 800 articles in the last two years. Fifty studies in recent years with the most relevant to the purpose of this study, which received the highest citations and in ISI journals.
Inclusion criteria: Studies with urine biopsy, at least 50 patients, exosome extraction.
Exclusion criteria: Studies on semen, blood or solid tissue and low density groups.
Results: EPI test with PCR examined the expression PCA3 (LncRNA), a family of ERG mRNAs (including TMPRSS2) and SPDEF in urinary exosomes are showed that these biomarkers prevent up to 30% of unnecessary primary and secondary biopsies in people with PSA 2- 10 and identified individuals with HGPCa grade (Gleason score 7 or higher) in this range of PSA and offers a new more accurate classification of PCa. Overexpression of these mRNA; ITSN1, ANXA3, and SLC45A3 from a seven-panel was more significant than the ten, five, and four-panel mRNA in prostate cancer diagnosis. miR-375-3p and miR-574-3p were introduced as more efficient (due to hybrid formation). Multivariable research of 7 mRNA panel, 2 microRNA panel, PCA3 value, age, serum PSA, prostate volume, and DRE result was evaluated with P-value 2.27 × 10^-82 and introduced as a PCa detection tool. Evaluation of increase in urinary exomiRs by lectin induced aggregation method miR-21-5p, miR-141-5p and miR-574-3p and decrease in HSA-miR-21-5p, HSA-miR-326, HSA-miR-375, HSA-miR-574-3p, HSA-miR-2110, besides measurement of miR-196a-5p, miR-501-3p, miR-19, miR-145 and miR-2909 by deep sequencing and then confirmation by PCR, miR-196a -5p, miR-501-3p, miR-451a, miR-486-3p, miR-486-5p, miR-532-5p, miR-26a-5p, miR-99b-3p ,and circ_0044516 by NGS and then rt-qPCR, which are upregulated in PCa, and also check the level of miR-21, miR-204, miR-375, miR-125, miR-1290, miR-572, miR-143-3p, miR-92-a1-5p, miR125-b,miR-107, miR-34a, miR-483-5p and lncRNA panel (MALAT1 + PCAT-1 + SPRY4-IT1) are suitable diagnostic biomarkers for prostate cancer.
It seems that detection of two urinary exomiRs HSA-miR-6090 and HSA-miR-3665 in PCa and normal groups compared by hydrogel-based hybridization chain reaction(HCR) are a robust diagnostic approach in PCa. MiR-30b-3p and miR-126-3p were validated by the Microarray method in diagnosis of prostate cancer.
Conclusion: Early detection of PCa by urinary exomiRs has so far helped more than 50,000 patients, but the current information is still insufficient for widespread clinical use, until more advancement of personalized medicine and more efficient and independent panels.