New Molecular Markers for Prostate Cancer Diagnosis
Urology Journal,
Vol. 21 No. 01 (2024),
28 February 2024
,
Page 1-13
https://doi.org/10.22037/uj.v20i.7687
Abstract
Purpose: Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth leading cause of
cancer death among men worldwide. Biomarkers are an important tool in the early detection of PCa. Prostate-specific antigen (PSA) is one of the oldest biomarkers for the early detection of PCa. Digital rectal exam (DRE) is
another screening test for PCa detection, which is considered as an irritating experience for patients. Biopsy is still
the most reliable method for PCa diagnosis; however, patients are prone to complications. Therefore, developing
non-invasive and accurate methods for PCa screening seems urgent to avoid unnecessary biopsies. There has been
remarkable development in PCa molecular biomarkers discovery, largely through progress in omics technologies.
Due to the many benefits of liquid biopsies, a significant set of PCa diagnostic kits have been developed using urine
samples. Despite the unique benefits of these kits, there are still many challenges to their widespread use in clinics.
Here, we have reviewed the latest developments of PCa biomarkers in liquid biopsies.
Methods: Literature on biomarkers for diagnosis of PCa was reviewed during the past two decades.
Results: PSA, PHI, PCA3, and 4K score are among the commonly used markers for PCa diagnosis which have
been used over a long-moderate length of time with multiple studies on their performance. We performed a review
of their performance. Newer markers are among RNA and DNA markers. Multiple non-coding RNAs (mi-RNAs)
were reviewed and their performance on Pca diagnosis was reviewed. Long noncoding RNAs (Lnc RNAs) including
PlncRNA-1, HOTAIR, SchLAP-1, MALAT1, MEG3, and PRCAT17.3 were summarized. mRNA markers
including TMPRSS2:ERG, and HOXC6 were presented. DNA-based markers including PTEN, HOXB13, and
BRCA2 were reviewed. Finally, the use of CircRNAs was reviewed for PCa diagnosis.
Conclusion: Many reviewed RNA-based biomarkers have promising results in the diagnosis of PCa.
- Prostate cancer, PSA, Non-invasive biomarkers, Liquid biopsy, Molecular biomarkers
How to Cite
References
Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent global patterns in prostate cancer incidence and mortality rates. European urology. 2020;77(1):38-52.
Hassanipour-Azgomi S, Mohammadian-Hafshejani A, Ghoncheh M, Towhidi F, Jamehshorani S, Salehiniya H. Incidence and mortality of prostate cancer and their relationship with the Human Development Index worldwide. Prostate international. 2016;4(3):118-124.
Basiri A, Eshrati B, Zarehoroki A, et al. Incidence, Gleason Score and Ethnicity Pattern of Prostate Cancer in the Multi-ethnicity Country of Iran During 2008-2010. Urol J. 2020;17(6):602-606.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.
Humphrey PA. Histopathology of prostate cancer. Cold Spring Harbor perspectives in medicine. 2017;7(10):a030411.
Hayes B, Murphy C, Crawley A, O’Kennedy R. Developments in point-of-care diagnostic technology for cancer detection. Diagnostics. 2018;8(2):39.
Ghayour-Mobarhan M, Ferns GA, Moghbeli M. Genetic and molecular determinants of prostate cancer among Iranian patients: An update. Critical reviews in clinical laboratory sciences. 2020;57(1):37-53.
Jones D, Friend C, Dreher A, Allgar V, Macleod U. The diagnostic test accuracy of rectal examination for prostate cancer diagnosis in symptomatic patients: a systematic review. BMC family practice. 2018;19(1):1-6.
Tomlins SA, Day JR, Lonigro RJ, et al. Urine TMPRSS2: ERG plus PCA3 for individualized prostate cancer risk assessment. European urology. 2016;70(1):45-53.
Litwin MS, Tan H-J. The diagnosis and treatment of prostate cancer: a review. Jama. 2017;317(24):2532-2542.
Bokhorst LP, Lepistö I, Kakehi Y, et al. Complications after prostate biopsies in men on active surveillance and its effects on receiving further biopsies in the Prostate cancer Research International: Active Surveillance (PRIAS) study. BJU international. 2016;118(3):366-371.
O'Connor LP, Lebastchi AH, Horuz R, et al. Role of multiparametric prostate MRI in the management of prostate cancer. World J Urol. 2021;39(3):651-659.
Pardini B, Sabo AA, Birolo G, Calin GA. Noncoding RNAs in extracellular fluids as cancer biomarkers: the new frontier of liquid biopsies. Cancers. 2019;11(8):1170.
Fujita K, Nonomura N. Urinary biomarkers of prostate cancer. International Journal of Urology. 2018;25(9):770-779.
Jing J, Gao Y. Urine biomarkers in the early stages of diseases: current status and perspective. Discovery medicine. 2018;25(136):57-65.
Ghorbanmehr N, Gharbi S, Korsching E, Tavallaei M, Einollahi B, Mowla SJ. miR‐21‐5p, miR‐141‐3p, and miR‐205‐5p levels in urine—promising biomarkers for the identification of prostate and bladder cancer. The Prostate. 2019;79(1):88-95.
Barnett CL, Tomlins SA, Underwood DJ, et al. Two-stage biomarker protocols for improving the precision of early detection of prostate cancer. Medical Decision Making. 2017;37(7):815-826.
Donovan M, Noerholm M, Bentink S, et al. A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate cancer and prostatic diseases. 2015;18(4):370-375.
McKiernan J, Donovan MJ, O’Neill V, et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA oncology. 2016;2(7):882-889.
Wang W-LW, Sorokin I, Aleksic I, et al. Expression of small noncoding RNAs in urinary exosomes classifies prostate cancer into indolent and aggressive disease. The Journal of urology. 2020;204(3):466-475.
Christensson A, Laurell CB, Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem. 1990;194(3):755-63.
Christensson A, Björk T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993;150(1):100-5.
Catalona WJ, Partin AW, Slawin KM, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. Jama. May 20 1998;279(19):1542-7. doi:10.1001/jama.279.19.1542
Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS. A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology. 2006;67(4):762-8.
Mikolajczyk SD, Millar LS, Wang TJ, et al. A Precursor Form of Prostate-specific Antigen Is More Highly Elevated in Prostate Cancer Compared with Benign Transition Zone Prostate Tissue. Cancer Research. 2000;60(3):756-759.
Sokoll LJ, Chan DW, Mikolajczyk SD, et al. Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis. Urology. 2003;61(2):274-6.
Semjonow A, Köpke T, Eltze E, Pepping-Schefers B, Bürgel H, Darte C. Pre-analytical in-vitro stability of [-2]proPSA in blood and serum. Clin Biochem. 2010;43(10-11):926-8.
Catalona WJ, Partin AW, Sanda MG, et al. A Multicenter Study of [-2]Pro-Prostate Specific Antigen Combined With Prostate Specific Antigen and Free Prostate Specific Antigen for Prostate Cancer Detection in the 2.0 to 10.0 ng/ml Prostate Specific Antigen Range. Journal of Urology. 2011;185(5):1650-1655.
Lazzeri M, Haese A, de la Taille A, et al. Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study. Eur Urol. 2013;63(6):986-94.
Vickers AJ, Cronin AM, Aus G, et al. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden. BMC Med. 2008;6:19.
Parekh DJ, Punnen S, Sjoberg DD, et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015;68(3):464-70.
Dhondt B, Geeurickx E, Tulkens J, et al. Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine. J Extracell Vesicles. 2020;9(1):1736935.
Zadra G, Photopoulos C, Loda M. The fat side of prostate cancer. Biochim Biophys Acta. 2013;1831(10):1518-32.
Senga S, Kobayashi N, Kawaguchi K, Ando A, Fujii H. Fatty acid-binding protein 5 (FABP5) promotes lipolysis of lipid droplets, de novo fatty acid (FA) synthesis and activation of nuclear factor-kappa B (NF-κB) signaling in cancer cells. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(9):1057-1067.
Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. Jul 29 2008;105(30):10513-8. doi:10.1073/pnas.0804549105
Chen ZH, Zhang GL, Li HR, et al. A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate. 15 2012;72(13):1443-52.
Mihelich BL, Maranville JC, Nolley R, Peehl DM, Nonn L. Elevated serum microRNA levels associate with absence of high-grade prostate cancer in a retrospective cohort. PLoS One. 2015;10(4):e0124245.
Selth LA, Townley S, Gillis JL, et al. Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease. Int J Cancer. 2012;131(3):652-61.
Nguyen HC, Xie W, Yang M, et al. Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer. Prostate. 2013;73(4):346-54.
Sharova E, Grassi A, Marcer A, et al. A circulating miRNA assay as a first-line test for prostate cancer screening. Br J Cancer. Jun 14 2016;114(12):1362-6. doi:10.1038/bjc.2016.151
Al-Qatati A, Akrong C, Stevic I, et al. Plasma microRNA signature is associated with risk stratification in prostate cancer patients. Int J Cancer. 2017;141(6):1231-1239.
Salido-Guadarrama AI, Morales-Montor JG, Rangel-Escareño C, et al. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone. Mol Med Rep. 2016;13(6):4549-60.
Fredsøe J, Rasmussen AKI, Thomsen AR, et al. Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine. Eur Urol Focus. 2018;4(6):825-833.
Pashaei E, Pashaei E, Ahmady M, Ozen M, Aydin N. Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy. PLoS One. 2017;12(6):e0179543.
Metcalf GAD, Shibakawa A, Patel H, et al. Amplification-Free Detection of Circulating microRNA Biomarkers from Body Fluids Based on Fluorogenic Oligonucleotide-Templated Reaction between Engineered Peptide Nucleic Acid Probes: Application to Prostate Cancer Diagnosis. Analytical Chemistry. 2016;88(16):8091-8098.
Lorenc T, Klimczyk K, Michalczewska I, Słomka M, Kubiak-Tomaszewska G, Olejarz W. Exosomes in Prostate Cancer Diagnosis, Prognosis and Therapy. Int J Mol Sci. 2020;21(6)
Li Z, Ma YY, Wang J, et al. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther. 2016;9:139-48.
Huang X, Yuan T, Liang M, et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol. 2015;67(1):33-41.
Foj L, Ferrer F, Serra M, et al. Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis. Prostate. 2017;77(6):573-583.
Kanagasabai T, Li G, Shen TH, et al. MicroRNA-21 deficiency suppresses prostate cancer progression through downregulation of the IRS1-SREBP-1 signaling pathway. Cancer Lett. 2022;525:46-54.
Samsonov R, Shtam T, Burdakov V, et al. Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: Application for prostate cancer diagnostic. Prostate. 2016;76(1):68-79.
Alhasan AH, Kim DY, Daniel WL, et al. Scanometric microRNA array profiling of prostate cancer markers using spherical nucleic acid-gold nanoparticle conjugates. Anal Chem. 2012;84(9):4153-60.
Alhasan AH, Scott AW, Wu JJ, et al. Circulating microRNA signature for the diagnosis of very high-risk prostate cancer. Proc Natl Acad Sci U S A. 2016;113(38):10655-60.
Mitra A, Fisher C, Foster CS, et al. Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. Br J Cancer. 2008;98(2):502-7.
De Marzo AM, DeWeese TL, Platz EA, et al. Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment. J Cell Biochem. 2004;91(3):459-77.
Lemos AE, Ferreira LB, Batoreu NM, de Freitas PP, Bonamino MH, Gimba ER. PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells. Tumour Biol. 2016;37(8):11339-48.
Chevli KK, Duff M, Walter P, et al. Urinary PCA3 as a predictor of prostate cancer in a cohort of 3,073 men undergoing initial prostate biopsy. J Urol. 2014;191(6):1743-8.
Li M, Zhou D, Zhang W, Gao S, Zhou X. Urine PCA3 mRNA level in diagnostic of prostate cancer. J Cancer Res Ther. 2018;14(4):864-866.
Merola R, Tomao L, Antenucci A, et al. PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience. J Exp Clin Cancer Res. 2015;34(1):15.
Cui Z, Ren S, Lu J, et al. The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol. 2013;31(7):1117-23.
Jin Y, Cui Z, Li X, Jin X, Peng J. Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer. Oncotarget. 2017;8(16):26090-26099.
Zhang A, Zhao JC, Kim J, et al. LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer. Cell Rep. 2015;13(1):209-221.
Prensner JR, Iyer MK, Sahu A, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet. 2013;45(11):1392-8.
Böttcher R, Hoogland AM, Dits N, et al. Novel long non-coding RNAs are specific diagnostic and prognostic markers for prostate cancer. Oncotarget. 2015;6(6):4036-50.
Mehra R, Shi Y, Udager AM, et al. A novel RNA in situ hybridization assay for the long noncoding RNA SChLAP1 predicts poor clinical outcome after radical prostatectomy in clinically localized prostate cancer. Neoplasia. 2014;16(12):1121-7.
Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22(39):8031-41.
Sowalsky AG, Xia Z, Wang L, et al. Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer. Mol Cancer Res. Jan 2015;13(1):98-106.
Ren S, Liu Y, Xu W, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 2013;190(6):2278-87. doi:10.1016/j.juro.2013.07.001
Wang F, Ren S, Chen R, et al. Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer. Oncotarget. 2014;5(22):11091-102.
Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48(3):R45-53.
Bayat H, Narouie B, Ziaee SM, Mowla SJ. Two long non-coding RNAs, Prcat17.3 and Prcat38, could efficiently discriminate benign prostate hyperplasia from prostate cancer. Prostate. 2018;78(11):812-818.
Yu J, Yu J, Mani RS, et al. An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer Cell. 2010;17(5):443-54.
Wang Z, Wang Y, Zhang J, et al. Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Mol Med Rep. 2017;16(4):5450-5458.
Gasi Tandefelt D, Boormans J, Hermans K, Trapman J. ETS fusion genes in prostate cancer. Endocr Relat Cancer. 2014;21(3):R143-52.
Kissick HT, On ST, Dunn LK, et al. The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells. BMC Cancer. 2015;15(1):604.
Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644-8.
St John J, Powell K, Conley-Lacomb MK, Chinni SR. TMPRSS2-ERG Fusion Gene Expression in Prostate Tumor Cells and Its Clinical and Biological Significance in Prostate Cancer Progression. J Cancer Sci Ther. 2012;4(4):94-101.
Deplus R, Delliaux C, Marchand N, et al. TMPRSS2-ERG fusion promotes prostate cancer metastases in bone. Oncotarget. 2017;8(7):11827-11840.
Tomlins SA, Bjartell A, Chinnaiyan AM, et al. ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol. 2009;56(2):275-86.
Sanguedolce F, Cormio A, Brunelli M, et al. Urine TMPRSS2: ERG Fusion Transcript as a Biomarker for Prostate Cancer: Literature Review. Clin Genitourin Cancer. 2016;14(2):117-21.
Tomlins SA, Day JR, Lonigro RJ, et al. Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment. Eur Urol. 2016;70(1):45-53.
Zhou J, Yang X, Song P, Wang H, Wang X. HOXC6 in the prognosis of prostate cancer. Artificial Cells, Nanomedicine, and Biotechnology. 2019;47(1):2715-2720.
Leyten GHJM, Hessels D, Smit FP, et al. Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer. Clin Cancer Res. 2015;21(13):3061-3070.
Hamid ARAH, Hoogland AM, Smit F, et al. The role of HOXC6 in prostate cancer development. The Prostate. 2015;75(16):1868-1876.
Yip PY. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):165-76.
Crumbaker M, Khoja L, Joshua AM. AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers (Basel). 2017;9(4)
Dong JT. Chromosomal deletions and tumor suppressor genes in prostate cancer. Cancer Metastasis Rev. 2001;20(3-4):173-93. doi:10.1023/a:1015575125780
Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009;4:127-50.
Yoshimoto M, Cunha IW, Coudry RA, et al. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer. 2007;97(5):678-85.
Stone L. The IMPACT of BRCA2 in prostate cancer. Nature Reviews Urology. 2019;16(11):639-639.
Jacky Lam WK, Dennis Lo YM. Circular RNAs as Urinary Biomarkers. Clinical Chemistry. 2019;65(10):1196-1198.
Vo JN, Cieslik M, Zhang Y, et al. The Landscape of Circular RNA in Cancer. Cell. 2019;176(4):869-881.e13.
Luo J, Li Y, Zheng W, et al. Characterization of a Prostate- and Prostate Cancer-Specific Circular RNA Encoded by the Androgen Receptor Gene. Molecular Therapy - Nucleic Acids. 2019;18:916-926.
Fu X, Zhang W, Su Y, Lu L, Wang D, Wang H. MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer. Prostate. 2016;76(6):543-51.
Zhang C, Xiong J, Yang Q, et al. Profiling and bioinformatics analyses of differential circular RNA expression in prostate cancer cells. Future Sci OA. 2018;4(9):Fsoa340.
Li Z, Hu Y, Zeng Q, et al. Circular RNA MYLK promotes hepatocellular carcinoma progression by increasing Rab23 expression by sponging miR-362-3p. Cancer Cell International. 2019;19
Kong Z, Wan X, Zhang Y, et al. Androgen-responsive circular RNA circSMARCA5 is up-regulated and promotes cell proliferation in prostate cancer. Biochem Biophys Res Commun. 2017;493(3):1217-1223.
Greene J, Baird AM, Casey O, et al. Circular RNAs are differentially expressed in prostate cancer and are potentially associated with resistance to enzalutamide. Sci Rep. 2019;9(1):10739.
He Y-D, Tao W, He T, et al. A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/mL at initial biopsy. Molecular Cancer. 2021;20(1):96.
Li T, Sun X, Chen L. Exosome circ_0044516 promotes prostate cancer cell proliferation and metastasis as a potential biomarker. Journal of Cellular Biochemistry. 2020;121(3):2118-2126.
Luo J, Li Y, Zheng W, et al. Characterization of a Prostate- and Prostate Cancer-Specific Circular RNA Encoded by the Androgen Receptor Gene. Mol Ther Nucleic Acids. 2019;18:916-926.
Jiang H, Lv DJ, Song XL, Wang C, Yu YZ, Zhao SC. Upregulated circZMIZ1 promotes the proliferation of prostate cancer cells and is a valuable marker in plasma. Neoplasma. 2020;67(1):68-77.
Litwin MS, Tan HJ. The Diagnosis and Treatment of Prostate Cancer: A Review. Jama. 2017;317(24):2532-2542.
Anceschi U, Tuderti G, Lugnani F, et al. Novel Diagnostic Biomarkers of Prostate Cancer: An Update. Curr Med Chem. 2019;26(6):1045-1058.
Adamaki M, Zoumpourlis V. Prostate Cancer Biomarkers: From diagnosis to prognosis and precision-guided therapeutics. Pharmacol Ther. 2021;228:107932.
- Abstract Viewed: 716 times
- 7687/pdf Downloaded: 350 times