Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-25T05:10:58.211Z Has data issue: false hasContentIssue false

Review of novel liquid-based biomarkers for prostate cancer: towards personalised and targeted medicine

Published online by Cambridge University Press:  06 April 2021

Ernest Osei*
Affiliation:
Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, ON, Canada Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Stephanie Swanson
Affiliation:
Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, ON, Canada Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada
Ruth Francis
Affiliation:
Department of Biology, University of Waterloo, Waterloo, ON, Canada
*
Author for correspondence: Dr Ernest Osei, Department of Medical Physics, Grand River Regional Cancer Centre, 835 King Street West, Kitchener, ON, N2G 1G3, Canada. Tel: 519 749 4300. E-mail: ernest.osei@grhosp.onca

Abstract

Background:

Prostate cancer is the most commonly diagnosed cancer in men and it is responsible for about 10% of all cancer mortalities in both American and Canadian men. At present, serum prostate-specific antigen levels remain the most commonly used test to detect prostate cancer, and the standard and definitive diagnosis of the disease is via prostate biopsy. Conventional tissue biopsies are usually invasive, expensive, painful, time-consuming, and unsuitable for screening and need to be consistently evaluated by expert pathologists and have limited repeatability. Consequently, liquid biopsies are emerging as a favourable alternative to conventional tissue biopsies, providing a non-invasive and cost-effective approach for screening, diagnosis, treatment and monitoring of prostate cancer patients.

Materials and methods:

We searched several databases from August to December 2020 for relevant studies published in English between 2000 and 2020 and reporting on liquid-based biomarkers available in detectable quantities in patient bodily fluid samples. In this narrative review paper, we describe seven novel and promising liquid-based biomarkers that potentially account for individual patient variability as well as used in disease risk assessment, screening for early disease detection and diagnosis, identification of patients’ risk for metastatic disease and subsequent relapse, monitoring patient response to specific treatment and providing clinicians the potential to stratify patients likely to benefit from a particular treatment.

Conclusions:

The concept of precision medicine from prevention to treatment techniques that take individual patient variability into account will depend on the development of effective clinical biomarkers that interrogate key aberrant pathways potentially targetable with molecular targets or immunologic therapies. Liquid-based biomarkers with high sensitivity and specificity for prostate cancer are emerging as minimally invasive, lower risk, readily obtainable and easily repeatable technique for screening for early disease detection and diagnosis, patient stratification at diagnosis into different risk categories, identification of patients’ risk for metastatic disease and subsequent relapse, and real-time monitoring of patient response to specific treatment. Thus, effective liquid-based biomarkers will potentially shift the treatment paradigm of prostate cancer towards more personalised and targeted medicine.

Type
Literature Review
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Canadian Cancer Society. Prostate cancer statistics. https://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=on. Accessed on 17th April 2020.Google Scholar
Brenner, D R, Weir, H K, Demers, A A et al. Projected estimates of cancer in Canada in 2020. CMAJ 2020; 192 (9): e199e205.CrossRefGoogle ScholarPubMed
Siegel, R L, Miller, K D, Jemal, A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70 (1): 730.CrossRefGoogle ScholarPubMed
Osei, E, Swanson, S. A review of current clinical biomarkers for prostate cancer: towards personalised and targeted therapy. J Radiother Pract 2020; 110 (Online Publication).Google Scholar
Osei, E, Swanson, S, Ibrahim, N, Sheraz, L. Review of novel tissue-based biomarkers for prostate cancers: towards personalised and targeted medicine. J Radiother Pract 2021 (in Press).Google Scholar
Bourdoumis, A, Papatsoris, A G, Chrisofos, M, Efstathiou, E, Skolarikos, A, Deliveliotis, C. The novel prostate cancer antigen 3 (PCA3) biomarker. Int Braz J Urol 2010; 36 (6): 665669.CrossRefGoogle ScholarPubMed
Cao, L, Lee, C H, Ning, J, Handy, B C, Wagar, E A, Meng, Q H. Combination of prostate cancer antigen 3 and prostate-specific antigen improves diagnostic accuracy in men at risk of prostate cancer. Arch Pathol Lab Med 2018; 142 (9): 11061112.CrossRefGoogle ScholarPubMed
Filella, X, Fernández-Galan, E, Bonifacio, R F, Foj, L. Emerging biomarkers in the diagnosis of prostate cancer. Pharmgenomics Pers Med 2018; 11: 8394.Google ScholarPubMed
Zappala, S M, Dong, Y, Linder, V et al. The 4Kscore blood test accurately identifies men with aggressive prostate cancer prior to prostate biopsy with or without DRE information. Int J Clin Pract Suppl 2017; 71 (6): e12943.CrossRefGoogle ScholarPubMed
Alford, A V, Brito, J M, Yadav, K K, Yadav, S S, Tewari, A K, Renzulli, J. The use of biomarkers in prostate cancer screening and treatment. Rev Urol 2017; 19 (4): 221234.Google ScholarPubMed
Hong, S K. Kallikreins as biomarkers for prostate cancer. Biomed Res Int 2014; 2014: 10.CrossRefGoogle ScholarPubMed
Punnen, S, Pavan, N, Parekh, D J. Finding the wolf in sheep’s clothing: the 4Kscore is a novel blood test that can accurately identify the risk of aggressive prostate cancer. Rev Urol 2015; 17 (1): 313.Google ScholarPubMed
Foley, R W, Gorman, L, Sharifi, N et al. Improving multivariable prostate cancer risk assessment using the Prostate Health Index. BJU Int 2016; 117 (3): 409417.CrossRefGoogle ScholarPubMed
Fossati, N, Lazzeri, M, Haese, A et al. Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study. BJU Int 2015; 115 (6): 913920.Google ScholarPubMed
Hsieh, P F, Chang, C H, Yang, C R et al. Prostate Health Index (PHI) improves prostate cancer detection at initial biopsy in Taiwanese men with PSA 4–10 ng/mL. Kaohsiung J Med Sci 2018; 34 (8): 461466.CrossRefGoogle ScholarPubMed
Lepor, A, Catalona, W J, Loeb, S. The Prostate Health Index: its utility in prostate cancer detection. Urol Clin North Am 2016; 43 (1): 16.CrossRefGoogle ScholarPubMed
Loeb, S, Catalona, W J. The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol 2014; 6 (2): 7477.CrossRefGoogle ScholarPubMed
Reed, A B, Parekh, D J. Biomarkers for prostate cancer detection. Expert Rev Anticancer Ther 2010; 10 (1): 103114.CrossRefGoogle ScholarPubMed
Hu, B, Yang, H, Yang, H. Diagnostic value of urine prostate cancer antigen 3 test using a cutoff value of 35 μg/L in patients with prostate cancer. Tumor Biol 2014; 35 (9): 85738580.Google ScholarPubMed
White, J, Shenoy, B V, Tutrone, R F et al. Clinical utility of the Prostate Health Index (phi) for biopsy decision management in a large group urology practice setting. Prostate Cancer Prostatic Dis 2017; 21 (1): 7884.CrossRefGoogle Scholar
Kremer, C L, Klein, R R, Mendelson, J et al. Expression of mTOR signaling pathway markers in prostate cancer progression. Prostate 2006; 66 (11): 12031212.CrossRefGoogle ScholarPubMed
Osei, E, Lumini, J, Gunasekara, D et al. A review of predictive, prognostic and diagnostic biomarkers for non-small-cell lung cancer: towards personalised and targeted cancer therapy. J Radiother Pract 2019; 19(4): 370384. doi: 10.1017/S1460396919000876 CrossRefGoogle Scholar
Osei, E, Walters, P, Masella, O et al. A review of predictive, prognostic and diagnostic biomarkers for brain tumors: towards personalised and targeted cancer therapy. J Radiother Pract 2019; 116 (Online Publication).Google Scholar
Fox, B P, Tabone, C J, Kandpal, R P. Potential clinical relevance of Eph receptors and ephrin ligands expressed in prostate carcinoma cell lines. Mol Cell Biol Res Commun 2006; 342 (4): 12631272.Google ScholarPubMed
Lisle, J E, Mertens-Walker, I, Rutkowski, R, Herington, A C, Stephenson, S. Eph receptors and their ligands: promising molecular biomarkers and therapeutic targets in prostate cancer. Biochim Biophys Acta Rev Cancer 2013; 1835 (2): 243257.CrossRefGoogle ScholarPubMed
Astin, J W, Batson, J, Kadir, S et al. Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells. Nat Cell Biol 2010; 12 (12): 11941204.CrossRefGoogle ScholarPubMed
Li, S, Zhao, Y, Chen, W et al. Exosomal ephrinA2 derived from serum as a potential biomarker for prostate cancer. J Cancer 2018; 9 (15): 26592665.CrossRefGoogle ScholarPubMed
Merlos-Suárez, A, Batlle, E. Eph–ephrin signalling in adult tissues and cancer. Curr Opin Cell Biol 2008; 20 (2): 194200.CrossRefGoogle ScholarPubMed
Surawska, H, Ma, P C, Salgia, R. The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev 2004; 15 (6): 419433.CrossRefGoogle ScholarPubMed
Xi, H, Wu, X, Wei, B, Chen, L. Eph receptors and ephrins as targets for cancer therapy. J Cell Mol Med 2012; 16 (12): 28942909.CrossRefGoogle ScholarPubMed
Wang, J, Zheng, X, Peng, Q, Zhang, X, Qin, Z. Eph receptors: the bridge linking host and virus. Cell Mol Life Sci 2019; 77 (12): 23552365.CrossRefGoogle Scholar
Taddei, M L, Parri, M, Angelucci, A et al. Kinase-dependent and -independent roles of EphA2 in the regulation of prostate cancer invasion and metastasis. Am J Pathol 2009; 174 (4): 14921503.CrossRefGoogle ScholarPubMed
Salem, A F, Gambini, L, Billet, S et al. Prostate cancer metastases are strongly inhibited by agonistic Epha2 ligands in an orthotopic mouse model. Cancers 2020; 12 (10): 2854.CrossRefGoogle Scholar
Li, S, Zhu, Y, Ma, C et al. Downregulation of EphA5 by promoter methylation in human prostate cancer. BMC cancer 2015; 15: 18.CrossRefGoogle ScholarPubMed
Petty, A, Myshkin, E, Qin, H et al. A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo. PloS One 2012; 7 (8): e42120.CrossRefGoogle ScholarPubMed
Li, S, Wu, Z, Chen, Y et al. Diagnostic and prognostic value of tissue and circulating levels of Ephrin-A2 in prostate cancer. Tumor Biol 2016; 37 (4): 53655374.CrossRefGoogle ScholarPubMed
Laborde, E. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ 2010; 17 (9): 13731380.CrossRefGoogle ScholarPubMed
Schnekenburger, M, Karius, T, Diederich, M. Regulation of epigenetic traits of the glutathione S-transferase P1 gene: from detoxification toward cancer prevention and diagnosis. Front Pharmacol 2014; 5: 170.CrossRefGoogle ScholarPubMed
Zhou, X, Jiao, D, Dou, M et al. Association of glutathione-S-transferase p1 gene promoter methylation and the incidence of prostate cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 2019; 145 (8): 19391948.CrossRefGoogle ScholarPubMed
Mahon, K L, Qu, W, Lin, H et al. Serum free methylated glutathione S-transferase 1 DNA levels, survival, and response to docetaxel in metastatic, castration-resistant prostate cancer: post hoc analyses of data from a phase 3 trial. Eur Urol 2019; 76 (3): 306312.CrossRefGoogle ScholarPubMed
Mian, O Y, Khattab, M H, Hedayati, M et al. GSTP1 loss results in accumulation of oxidative DNA base damage and promotes prostate cancer cell survival following exposure to protracted oxidative stress. Prostate 2016; 76 (2): 199206.CrossRefGoogle ScholarPubMed
Martignano, F, Gurioli, G, Salvi, S et al. GSTP1 methylation and protein expression in prostate cancer: diagnostic implications. Dis Markers 2016; 2016: 4358292.CrossRefGoogle ScholarPubMed
Bastian, P J, Palapattu, G S, Lin, X et al. Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res 2005; 11 (11): 40374043.CrossRefGoogle ScholarPubMed
Trock, B J. Application of metabolomics to prostate cancer. Urol Oncol 2011; 29 (5): 572581.CrossRefGoogle ScholarPubMed
Lima, A R, de Lourdes Bastos, M, Carvalho, M, de Pinho, P G. Biomarker discovery in human prostate cancer: an update in metabolomics studies. Transl Oncol 2016; 9 (4): 357370.CrossRefGoogle ScholarPubMed
Kdadra, M, Höckner, S, Leung, H, Kremer, W, Schiffer, E. Metabolomics biomarkers of prostate cancer: a systematic review. Diagnostics 2019; 9 (1): 21.CrossRefGoogle ScholarPubMed
Kelly, R S, Vander Heiden, M G, Giovannucci, E, Mucci, L A. Metabolomic biomarkers of prostate cancer: prediction, diagnosis, progression, prognosis, and recurrence. Cancer Epidemiol Biomarkers Prev 2016; 25 (6): 887906.CrossRefGoogle Scholar
Chaleckis, R, Murakami, I, Takada, J, Kondoh, H, Yanagida, M. Individual variability in human blood metabolites identifies age-related differences. Proc Natl Acad Sci U S A 2016; 113 (16): 42524259.CrossRefGoogle ScholarPubMed
Psychogios, N, Hau, D D, Peng, J et al. The human serum metabolome. PloS One 2011; 6 (2): e16957.CrossRefGoogle ScholarPubMed
Giskeødegård, G F, Hansen, A F, Bertilsson, H et al. Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia. Br J Cancer 2015; 113 (12): 17121719.CrossRefGoogle ScholarPubMed
Zang, X, Jones, C M, Long, T Q et al. Feasibility of detecting prostate cancer by ultraperformance liquid chromatography–mass spectrometry serum metabolomics. J Proteome Res 2014; 13 (7): 34443454.CrossRefGoogle ScholarPubMed
Röhnisch, H E, Kyrø, C, Olsen, A, Thysell, E, Hallmans, G, Moazzami, A A. Identification of metabolites associated with prostate cancer risk: a nested case-control study with long follow-up in the Northern Sweden Health and Disease Study. BMC Med 2020; 18 (1): 1187.CrossRefGoogle ScholarPubMed
Huang, J, Weinstein, S J, Moore, S C et al. Pre-diagnostic serum metabolomic profiling of prostate cancer survival. J Gerontol A Biol Sci Med Sci 2019; 74 (6): 853859.CrossRefGoogle ScholarPubMed
Schmidt, J A, Fensom, G K, Rinaldi, S et al. Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition. BMC Med 2017; 15: 122.CrossRefGoogle ScholarPubMed
Stabler, S, Koyama, T, Zhao, Z et al. Serum methionine metabolites are risk factors for metastatic prostate cancer progression. PloS One 2011; 6 (8): e22486.CrossRefGoogle ScholarPubMed
Verma, N, Chakraverty, J, Baweja, P, Girotra, A, Chatterjee, L, Chugh, M. Extremely high ferritinemia associated with haemophagocytic lympho histiocytosis (HLH). Ind J Clin Biochem 2016; 32 (1): 117120.CrossRefGoogle Scholar
Zhao, H, Zhao, X, Lei, T, Zhang, M. Screening, identification of prostate cancer urinary biomarkers and verification of important spots. Invest New Drugs 2019; 37 (5): 935947.CrossRefGoogle Scholar
Wang, X, An, P, Zeng, J et al. Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer. Oncotarget 2017; 8 (11): 1786217872.CrossRefGoogle ScholarPubMed
Su, Q, Lei, T, Zhang, M. Association of ferritin with prostate cancer. J BUON 2017; 22 (3): 766770.Google ScholarPubMed
Vela, D. Iron metabolism in prostate cancer; from basic science to new therapeutic strategies. Front Oncol 2018; 8: 547.CrossRefGoogle ScholarPubMed
Rouillon, J, Lefebvre, T, Denard, J et al. High urinary ferritin reflects myoglobin iron evacuation in DMD patients. Neuromuscul Disord 2018; 28 (7): 564571.CrossRefGoogle ScholarPubMed
Solé, C, Goicoechea, I, Goñi, A et al. The urinary transcriptome as a source of biomarkers for prostate cancer. Cancers 2020; 12 (2): 513.CrossRefGoogle ScholarPubMed
Kuvibidila, S R, Gauthier, T, Rayford, W. Serum ferritin levels and transferrin saturation in men with prostate cancer. J Natl Med Assoc 2004; 96 (5): 641649.Google ScholarPubMed
Koike, A, Robles, B E F, da Silva Bonacini, A G et al. Thiol groups as a biomarker for the diagnosis and prognosis of prostate cancer. Sci Rep 2020; 10: 9093.CrossRefGoogle ScholarPubMed
Bouchelouche, K, Choyke, P L, Capala, J. Prostate specific membrane antigen- a target for imaging and therapy with radionuclides. Discov Med 2010; 9 (44): 5561.Google ScholarPubMed
Zhang, L, Wang, C, Yang, R et al. Real-time quantitative RT-PCR assay of prostate-specific antigen and prostate-specific membrane antigen in peripheral blood for detection of prostate cancer micrometastasis. Urol Oncol 2008; 26 (6): 634640.CrossRefGoogle ScholarPubMed
Wüstemann, T, Haberkorn, U, Babich, J, Mier, W. Targeting prostate cancer: prostate-specific membrane antigen based diagnosis and therapy. Med Res Rev 2019; 39 (1): 4069.CrossRefGoogle ScholarPubMed
Ross, J S, Sheehan, C E, Fisher, H A G et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res 2003; 9 (17): 6357.Google ScholarPubMed
Paller, C J, Piana, D, Eshleman, J R et al. A pilot study of prostate-specific membrane antigen (PSMA) dynamics in men undergoing treatment for advanced prostate cancer. Prostate 2019; 79 (14): 15971603.CrossRefGoogle ScholarPubMed
Hupe, M C, Philippi, C, Roth, D et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol 2018; 8: 623.CrossRefGoogle ScholarPubMed
Ghosh, A, Heston, W. Understanding prostate-specific membrane antigen and its implication in prostate cancer. In: LaRochelle, W J, Shimkets, R A (eds). The Oncogenomics Handbook. Cancer Drug Discovery and Development. Totowa, NJ: Humana Press, 2005: 597615.Google Scholar
Chang, S S. Overview of prostate-specific membrane antigen. Rev Urol 2004; 6 (suppl 10), S13S18.Google ScholarPubMed
Xiao, Z, Adam, B L, Cazares, L H et al. Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease. Cancer Res 2001; 61 (16): 60296033.Google ScholarPubMed
Nagaya, N, Nagata, M, Lu, Y et al. Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer. PloS One 2020; 15 (1): e0226219.CrossRefGoogle ScholarPubMed
Park, Y H, Shin, H W, Jung, A R et al. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer. Sci Rep 2016; 6: 30386.CrossRefGoogle ScholarPubMed
Goto, Y, Kurozumi, A, Enokida, H, Ichikawa, T, Seki, N. Functional significance of aberrantly expressed microRNAs in prostate cancer. Int J Urol 2015; 22 (3): 242252.CrossRefGoogle ScholarPubMed
Massillo, C, Dalton, G N, Farré, P L, De Luca, P, De Siervi, A. Implications of microRNA dysregulation in the development of prostate cancer. Reproduction 2017; 154 (4): R81R97.CrossRefGoogle ScholarPubMed
Liu, W, Mao, S Y, Zhu, W Y. Impact of tiny miRNAs on cancers. World J Gastroenterol 2007; 13 (4): 497502.CrossRefGoogle ScholarPubMed
Bidarra, D, Constâncio, V, Barros-Silva, D et al. Circulating microRNAs as biomarkers for prostate cancer detection and metastasis development prediction. Front Oncol 2019; 9 (11): 900.CrossRefGoogle ScholarPubMed
Esquela-Kerscher, A, Slack, F J. Oncomirs — microRNAs with a role in cancer. Nat Rev Cancer 2006; 6 (4): 259269.CrossRefGoogle ScholarPubMed
Garzon, R, Calin, G A, Croce, C M. MicroRNAs in cancer. Annu Rev Med 2009; 60 (1): 167179.CrossRefGoogle ScholarPubMed
Ma, J, Dong, C, Ji, C. MicroRNA and drug resistance. Cancer Gene Ther 2010; 17 (8): 523531.Google ScholarPubMed
Wu, W, Sun, M, Zou, G, Chen, J. MicroRNA and cancer: current status and prospective. Int J Cancer 2006; 120 (5): 953960.CrossRefGoogle Scholar
Nelson, K M, Weiss, G J. MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther 2008; 7 (12): 36553660.CrossRefGoogle ScholarPubMed
Calin, G A, Croce, C M. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6 (11): 857866.CrossRefGoogle ScholarPubMed
Al-Kafaji, G, Said, H M, Alam, M A, Al Naieb, Z T. Blood-based microRNAs as diagnostic biomarkers to discriminate localized prostate cancer from benign prostatic hyperplasia and allow cancer-risk stratification. Oncol Lett 2018; 16 (1): 13571365.Google ScholarPubMed
Hoey, C, Ahmed, M, Fotouhi Ghiam, A et al. Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy. J Transl Med 2019; 17: 173.CrossRefGoogle ScholarPubMed
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): 3341.CrossRefGoogle ScholarPubMed
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): 2118.CrossRefGoogle Scholar
Pan, J, Ding, M, Xu, K, Yang, C, Mao, L. Exosomes in diagnosis and therapy of prostate cancer. Oncotarget 2017; 8 (57): 9769397700.CrossRefGoogle ScholarPubMed
Soekmadji, C, Russell, PJ, Nelson, CC. Exosomes in prostate cancer: putting together the pieces of a puzzle. Cancers 2013; 5 (4): 15221544.CrossRefGoogle ScholarPubMed
Kalluri, R, LeBleu, V S. The biology, function, and biomedical applications of exosomes. Science 2020; 367 (6478): eaau6977.CrossRefGoogle ScholarPubMed
Krishn, SR, Singh, A, Bowler, N et al. Prostate cancer sheds the αvβ3 integrin in vivo through exosomes. Matrix Biol 2019; 77: 4157.CrossRefGoogle ScholarPubMed
Gabriel, K, Ingram, A, Austin, R et al. Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer. PloS One 2013; 8 (7): e70047.CrossRefGoogle ScholarPubMed
Øverbye, A, Skotland, T, Koehler, C J et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget 2015; 6 (30): 3035730376.CrossRefGoogle ScholarPubMed
Khan, S, Jutzy, J M S, Valenzuela, M M A et al. Plasma-derived exosomal Survivin, a plausible biomarker for early detection of prostate cancer. PloS One 2012; 7 (10): e46737.CrossRefGoogle ScholarPubMed
Hao, N, Zhang, J X J. Microfluidic screening of circulating tumor biomarkers toward liquid biopsy. Sep Purif Rev 2018; 47 (1): 130.CrossRefGoogle Scholar
Chen, X, Ba, Y, Ma, L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18 (10): 9971006.Google ScholarPubMed
Sausen, M, Parpart, S, Diaz, L A. Circulating tumor DNA moves further into the spotlight. Genome Med 2014; 6 (5): 35.CrossRefGoogle ScholarPubMed
Perakis, S, Speicher, M R. Emerging concepts in liquid biopsies. BMC Med 2017; 15: 75.CrossRefGoogle ScholarPubMed