Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Genitourinary Tumors: Update on Molecular Biomarkers for Diagnosis, Prognosis and Prediction of Response to Therapy

Author(s): Alessia Cimadamore, Marina Scarpelli, Matteo Santoni, Francesco Massari, Francesca Tartari, Roy Cerqueti, Antonio Lopez-Beltran, Liang Cheng and Rodolfo Montironi*

Volume 20, Issue 4, 2019

Page: [305 - 312] Pages: 8

DOI: 10.2174/1389200220666190225124352

Price: $65

Abstract

Background: Research of biomarkers in genitourinary tumors goes along with the development of complex emerging techniques ranging from next generation sequencing platforms, applied to archival pathology specimens, cytological samples, liquid biopsies, and to patient-derived tumor models.

Methods: This contribution is an update on molecular biomarkers for diagnosis, prognosis and prediction of response to therapy in genitourinary tumors. The following major topics are dealt with: Immunological biomarkers, including the microbiome, and their potential role and caveats in renal cell carcinoma, bladder and prostate cancers and testicular germ cell tumors; Tissue biomarkers for imaging and therapy, with emphasis on Prostate-specific membrane antigen in prostate cancer; Liquid biomarkers in prostate cancer, including circulating tumor cell isolation and characterization in renal cell carcinoma, bladder cancer with emphasis on biomarkers detectable in the urine and testicular germ cell tumors; and Biomarkers and economic sustainability.

Conclusion: The identification of effective biomarkers has become a major focus in cancer research, mainly due to the necessity of selecting potentially responsive patients in order to improve their outcomes, as well as to reduce the toxicity and costs related to ineffective treatments.

Keywords: Genitourinary tumors, microbiome, renal cell carcinoma, prostate cancer, bladder cancer, liquid biopsy, PSMA, immunotherapy.

Graphical Abstract

[1]
Santoni, M.; Scarpelli, M.; Cheng, L.; Lopez-Beltran, A.; Massari, F.; Matrana, M.R.; Moch, H.; Montironi, R. Immunotargeting of genitourinary tumors: An overview. Curr. Drug Targets, 2016, 17(7), 750-756.
[2]
Santoni, M.; Massari, F.; Di Nunno, V.; Conti, A.; Cimadamore, A.; Scarpelli, M.; Montironi, R.; Cheng, L.; Battelli, N.; Lopez-Beltran, A. Immunotherapy in renal cell carcinoma: Latest evidence and clinical implications. Drugs Context, 2018, 7, 212528.
[3]
Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; Castellano, D.; Choueiri, T.K.; Gurney, H.; Donskov, F.; Bono, P.; Wagstaff, J.; Gauler, T.C.; Ueda, T.; Tomita, Y.; Schutz, F.A.; Kollmannsberger, C.; Larkin, J.; Ravaud, A.; Simon, J.S.; Xu, L.A.; Waxman, I.M.; Sharma, P. CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med., 2015, 373, 1803-1813.
[4]
Tannir, N.M.; Hammers, H.J.; Amin, A.; Grimm, M.O.; Rini, B.I.; Mekan, S.; McHenry, M.B.; Kollmannsberger, C.K. Characterization of the benefit-risk profile of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced renal cell carcinoma (aRCC; CheckMate 214). J. Clin. Oncol., 2018, 36, 686-686.
[5]
Gevaert, T.; Montironi, R.; Lopez-Beltran, A.; Van Leenders, G.; Allory, Y.; De Ridder, D.; Claessens, F.; Kockx, M.; Akand, M.; Joniau, S.; Netto, G.; Libbrecht, L. Genito-urinary genomics and emerging biomarkers for immunomodulatory cancer treatment. Semin. Cancer Biol., 2018, 52(Pt 2), 216-227.
[6]
Mann, S.A.; Lopez-Beltran, A.; Massari, F.; Pili, R.; Fiorentino, M.; Koch, M.O.; Kaimakliotis, H.Z.; Wang, L.; Scarpelli, M.; Ciccarese, C.; Moch, H.; Montironi, R.; Cheng, L. Targeting the programmed cell death-1 pathway in genitourinary tumors: Current progress and future perspectives. Curr. Drug Metab., 2017, 18(8), 700-711.
[7]
Kucharczyk, J.; Matrana, M.R.; Santoni, M.; Massari, F.; Scarpelli, M.; Cheng, L.; Lopez-Beltran, A.; Cascinu, S.; Montironi, R.; Holger, M. Emerging Immunotargets in metastatic renal cell carcinoma. Curr. Drug Targets, 2016, 17, 771-776.
[8]
Alsaab, H.O.; Sau, S.; Alzhrani, R.; Tatiparti, K.; Bhise, K.; Kashaw, S.K.; Iyer, A.K. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome. Front. Pharmacol., 2017, 8, 561.
[9]
Mazza, C.; Escudier, B.; Albiges, L. Nivolumab in renal cell carcinoma: Latest evidence and clinical potential. Ther. Adv. Med. Oncol., 2017, 9, 171-181.
[10]
Hirayama, Y.; Gi, M.; Yamano, S.; Tachibana, H.; Okuno, T.; Tamada, S.; Nakatani, T.; Wanibuchi, H. Anti-PD-L1 treatment enhances antitumor effect of everolimus in a mouse model of renal cell carcinoma. Cancer Sci., 2016, 107, 1736-1744.
[11]
Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; Miller, M.L.; Rekhtman, N.; Moreira, A.L.; Ibrahim, F.; Bruggeman, C.; Gasmi, B.; Zappasodi, R.; Maeda, Y.; Sander, C.; Garon, E.B.; Merghoub, T.; Wolchok, J.D.; Schumacher, T.N.; Chan, T.A. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015, 348(6230), 124-128.
[12]
Riaz, N.; Havel, J.J.; Kendall, S.M.; Makarov, V.; Walsh, L.A.; Desrichard, A.; Weinhold, N.; Chan, T.A. Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy. Nat. Genet., 2016, 48, 1327-1329.
[13]
Schumacher, T.N.; Schreiber, R.D. Neoantigens in cancer immunotherapy. Science, 2015, 348(6230), 69-74.
[14]
Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature, 2015, 523, 231-235.
[15]
Smyth, M.J.; Ngiow, S.F.; Ribas, A.; Teng, M.W. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat. Rev. Clin. Oncol., 2016, 13(3), 143-158.
[16]
Koyama, S.; Akbay, E.A.; Li, Y.Y.; Herter-Sprie, G.S.; Buczkowski, K.A.; Richards, W.G.; Gandhi, L.; Redig, A.J.; Rodig, S.J.; Asahina, H.; Jones, R.E.; Kulkarni, M.M.; Kuraguchi, M.; Palakurthi, S.; Fecci, P.E.; Johnson, B.E.; Janne, P.A.; Engelman, J.A.; Gangadharan, S.P.; Costa, D.B.; Freeman, G.J.; Bueno, R.; Hodi, F.S.; Dranoff, G.; Wong, K.K.; Hammerman, P.S. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun., 2016, 7, 10501.
[17]
Chovanec, M.; Cierna, Z.; Miskovska, V.; Machalekova, K.; Svetlovska, D.; Kalavska, K.; Rejlekova, K.; Spanik, S.; Kajo, K.; Babal, P.; Mardiak, J.; Mego, M. Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors. Oncotarget, 2017, 8, 21794-21805.
[18]
Adra, N.; Einhorn, L.H.; Althouse, S.K.; Ammakkanavar, N.R.; Musapatika, D.; Albany, C.; Vaughn, D.; Hanna, N.H. Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: A Hoosier Cancer Research Network Study GU14-206. Ann. Oncol., 2018, 29, 209-214.
[19]
Shen, H.; Shih, J.; Hollern, D.P.; Wang, L.; Bowlby, R.; Tickoo, S.K.; Thorsson, V.; Mungall, A.J.; Newton, Y.; Hegde, A.M.; Armenia, J.; Sánchez-Vega, F.; Pluta, J.; Pyle, L.C.; Mehra, R.; Reuter, V.E.; Godoy, G.; Jones, J.; Shelley, C.S.; Feldman, D.R.; Vidal, D.O.; Lessel, D.; Kulis, T.; Cárcano, F.M.; Leraas, K.M.; Lichtenberg, T.M.; Brooks, D.; Cherniack, A.D.; Cho, J.; Heiman, D.I.; Kasaian, K.; Liu, M.; Noble, M.S.; Xi, L.; Zhang, H.; Zhou, W. ZenKlusen, J.C.; Hutter, C.M.; Felau, I.; Zhang, J.; Schultz, N.; Getz, G.; Meyerson, M.; Stuart, J.M.; Cancer Genome Atlas Research Network, Akbani, R.; Wheeler, D.A.; Laird, P.W.; Nathanson, K.L.; Cortessis, V.K.; Hoadley, K.A. Integrated molecular characterization of testicular germ cell tumors. Cell Reports, 2018, 23, 3392-3406.
[20]
Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.P.M.; Alou, M.T.; Daillère, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; Fidelle, M.; Flament, C.; Poirier-Colame, V.; Opolon, P.; Klein, C.; Iribarren, K.; Mondragón, L.; Jacquelot, N.; Qu, B.; Ferrere, G.; Clémenson, C.; Mezquita, L.; Masip, J.R.; Naltet, C.; Brosseau, S.; Kaderbhai, C.; Richard, C.; Rizvi, H.; Levenez, F.; Galleron, N.; Quinquis, B.; Pons, N.; Ryffel, B.; Minard-Colin, V.; Gonin, P.; Soria, J.C.; Deutsch, E.; Loriot, Y.; Ghiringhelli, F.; Zalcman, G.; Goldwasser, F.; Escudier, B.; Hellmann, M.D.; Eggermont, A.; Raoult, D.; Albiges, L.; Kroemer, G.; Zitvogel, L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science, 2018, 359, 91-97.
[21]
Cani, P.D. Human gut microbiome: Hopes, threats and promises. Gut, 2018, 67, 1716-1725.
[22]
Cavarretta, I.; Ferrarese, R.; Cazzaniga, W.; Saita, D.; Lucianò, R.; Ceresola, E.R.; Locatelli, I.; Visconti, L.; Lavorgna, G.; Briganti, A.; Nebuloni, M.; Doglioni, C.; Clementi, M.; Montorsi, F.; Canducci, F.; Salonia, A. The microbiome of the prostate tumor microenvironment. Eur. Urol., 2017, 72, 625-631.
[23]
Sfanos, K.S.; Sauvageot, J.; Fedor, H.L.; Dick, J.D.; De Marzo, A.M.; Isaacs, W.B. A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms. Prostate, 2008, 68, 306-320.
[24]
Montironi, R.; Gasparrini, S.; Mazzucchelli, R.; Massari, F.; Cheng, L.; Lopez-Beltran, A.; Montorsi, F.; Scarpelli, M. Re: Karim A. Touijer, James A. Eastham. The sentinel lymph node concept and novel approaches in detecting lymph node metastasis in prostate cancer. Eur Urol 2016;70:738-9: Sentinel lymph nodes in adipose tissue surrounding the prostate gland and seminal vesicles as observed in virtual whole-mount histologic slides. Eur Urol 2017;71:e73-5. Eur. Urol., 2017, 72(2), e37-e38.
[25]
Montironi, R.; Lopez-Beltran, A.; Cheng, L.; Scarpelli, M.; Mazzucchelli, R.; Montorsi, F. Re: Antibody-drug conjugates targeting prostate-specific membrane antigen. Eur. Urol., 2014, 66(6), 1190-1193.
[26]
Wright, G.L. Jr1.; Grob, B.M.; Haley, C.; Grossman, K.; Newhall, K.; Petrylak, D.; Troyer, J.; Konchuba, A.; Schellhammer, P.F.; Moriarty, R. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology, 1996, 48(2), 326-334.
[27]
Cimadamore, A.; Scarpelli, M.; Cheng, L.; Lopez-Beltran, A.; Montorsi, F.; Montironi, R. Re: Isabel Rauscher, Charlotte Düwel, Bernhard Haller. Efficacy, predictive factors, and prediction nomograms for 68Ga-labeled prostate-specific membrane antigen-ligand positron-emission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur. Urol. 2018,73,656-61: Clinical Significance of Prostate-specific Membrane Antigen Immunohistochemistry and Role of the Uropathologists. Eur. Urol., 2018, 74(6), e141-e144.
[28]
Santoni, M.; Scarpelli, M.; Mazzucchelli, R.; Lopez-Beltran, A.; Cheng, L.; Cascinu, S.; Montironi, R. Targeting prostate-specific membrane antigen for personalized therapies in prostate cancer: Morphologic and molecular backgrounds and future promises. J. Biol. Regul. Homeost. Agents, 2014, 28(4), 555-563.
[29]
Rauscher, I.; Düwel, C.; Haller, B.; Rischpler, C.; Heck, M.M.; Gschwend, J.E.; Schwaiger, M.; Maurer, T.; Eiber, M. Efficacy, predictive factors, and prediction nomograms for 68Ga-labeled prostate-specific membrane antigen-ligand positronemission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur. Urol., 2018, 73(5), 656-661.
[30]
Cimadamore, A.; Cheng, M.; Santoni, M.; Lopez-Beltran, A.; Battelli, N.; Massari, F.; Galosi, A.B.; Scarpelli, M.; Montironi, R. New prostate cancer targets for diagnosis, imaging, and therapy: Focus on prostate-specific membrane antigen. Front. Oncol., 2018, 8, 653.
[31]
Hope, T.A.; Truillet, C.; Ehman, E.C.; Afshar-Oromieh, A.; Aggarwal, R.; Ryan, C.J.; Carroll, P.R.; Small, E.J.; Evans, M.J. 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition: First human experience. J. Nucl. Med., 2017, 58(1), 81-84.
[32]
Karachaliou, N.; Mayo-de-Las-Casas, C.; Molina-Vila, M.A.; Rosell, R. Real-time liquid biopsies become a reality in cancer treatment. Ann. Transl. Med., 2015, 3(3), 36.
[33]
Allard, W.J.; Matera, J.; Miller, M.C.; Repollet, M.; Connelly, M.C.; Rao, C.; Tibbe, A.G.; Uhr, J.W.; Terstappen, L.W. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin. Cancer Res., 2004, 10, 6897-6904.
[34]
Massari, F.; Di Nunno, V.; Comito, F.; Cubelli, M.; Ciccarese, C.; Iacovelli, R.; Fiorentino, M.; Montironi, R.; Ardizzoni, A. Circulating tumor cells in genitourinary tumors. Ther. Adv. Urol., 2017, 10(2), 65-77.
[35]
Lorente, D.; Olmos, D.; Mateo, J.; Dolling, D.; Bianchini, D.; Seed, G.; Flohr, P.; Crespo, M.; Figueiredo, I.; Miranda, S.; Scher, H.I.; Terstappen, L.W.M.M.; De Bono, J.S. Circulating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts. Ann. Oncol., 2018, 29, 1554-1560.
[36]
Miyamoto, D.T.; Lee, R.J.; Stott, S.L.; Wittner, B.S.; Ulman, M.; Smas, M.E.; Lord, J.B.; Brannigan, B.W.; Trautwein, J.; Bander, N.H.; Wu, C.L.; Sequist, L.V.; Smith, M.R.; Ramaswamy, S.; Toner, M.; Maheswaran, S.; Haber, D.A. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov., 2012, 2, 995-1003.
[37]
Wyatt, A.W.; Annala, M.; Aggarwal, R.; Beja, K.; Feng, F.; Youngren, J.; Foye, A.; Lloyd, P.; Nykter, M.; Beer, T.M.; Alumkal, J.J.; Thomas, G.V.; Reiter, R.E.; Rettig, M.B.; Evans, C.P.; Gao, A.C.; Chi, K.N.; Small, E.J.; Gleave, M.E. Concordance of circulating tumor DNA and matched metastatic tissue biopsy in prostate cancer. J. Natl. Cancer Inst., 2017, 109(12)
[http://dx.doi.org/10.1093/jnci/djx118]
[38]
Ciccarese, C.; Montironi, R.; Fiorentino, M.; Martignoni, G.; Brunelli, M.; Iacovelli, R.; Lopez-Beltran, A.; Cheng, L.; Scarpelli, M.; Moch, H.; Tortora, G.; Massari, F. Circulating Tumor Cells: A Reliable Biomarker for Prostate Cancer Treatment Assessment? Curr. Drug Metab., 2017, 18(8), 692-699.
[39]
Ross, R.W.; Galsky, M.D.; Scher, H.I.; Magidson, J.; Wassmann, K.; Lee, G.S.; Katz, L.; Subudhi, S.K.; Anand, A.; Fleisher, M.; Kantoff, P.W.; Oh, W.K. A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: A prospective study. Lancet Oncol., 2012, 13, 1105-1113.
[40]
Ulz, P.; Belic, J.; Graf, R.; Auer, M.; Lafer, I.; Fischereder, K.; Webersinke, G.; Pummer, K.; Augustin, H.; Pichler, M.; Hoefler, G.; Bauernhofer, T.; Geigl, J.B.; Heitzer, E. Speicher, M. R. Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer. Nat. Commun., 2016, 7, 12008.
[41]
Romanel, A.; Gasi Tandefelt, D.; Conteduca, V.; Jayaram, A.; Casiraghi, N.; Wetterskog, D.; Salvi, S.; Amadori, D.; Zafeiriou, Z.; Rescigno, P.; Bianchini, D.; Gurioli, G.; Casadio, V.; Carreira, S.; Goodall, J.; Wingate, A.; Ferraldeschi, R.; Tunariu, N.; Flohr, P.; De Giorgi, U.; de Bono, J.S.; Demichelis, F.; Attard, G. Plasma AR and abiraterone-resistant prostate cancer. Sci. Transl. Med., 2015, 7(312), 312re10.
[42]
Gorges, T.M.; Riethdorf, S.; Von Ahsen, O.; Nastał, Y. P.; Röck, K.; Boede, M.; Peine, S.; Kuske, A.; Schmid, E.; Kneip, C.; König, F.; Rudolph, M.; Pantel, K. Heterogeneous PSMA expression on circulating tumor cells: A potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer. Oncotarget, 2016, 7(23), 34930-34941.
[43]
Maetzel, D.; Denzel, S.; Mack, B.; Canis, M.; Went, P.; Benk, M.; Kieu, C.; Papior, P.; Baeuerle, P.A.; Munz, M.; Gires, O. Nuclear signalling by tumour-associated antigen EpCAM. Nat. Cell Biol., 2009, 11(2), 162-171.
[44]
Gradilone, A.; Iacovelli, R.; Cortesi, E.; Raimondi, C.; Gianni, W.; Nicolazzo, C.; Petracca, A.; Palazzo, A.; Longo, F.; Frati, L.; Gazzaniga, P. Circulating tumor cells and “suspicious objects” evaluated through CellSearch® in metastatic renal cell carcinoma. Anticancer Res., 2011, 31(12), 4219-4221.
[45]
Montironi, R.; Santoni, M.; Scarpelli, M.; Piva, F.; Lopez-Beltran, A.; Cheng, L.; Briganti, A.; Montorsi, F. Re: Epithelial-to-mesenchymal transition in renal neoplasms. Eur. Urol., 2015, 68(4), 736-737.
[46]
Piva, F.; Giulietti, M.; Santoni, M.; Occhipinti, G.; Scarpelli, M.; Lopez-Beltran, A.; Cheng, L.; Principato, G.; Montironi, R. Epithelial to mesenchymal transition in renal cell carcinoma: Implications for cancer therapy. Mol. Diagn. Ther., 2016, 20(2), 111-117.
[47]
Hanna, S.M.; Kirk, P.; Holt, O.J.; Puklavec, M.J.; Brown, M.H.; Barclay, A.N. A novel form of the membrane protein CD147 that contains an extra Ig-like domain and interacts homophilically. BMC Biochem., 2003, 4, 17.
[48]
Liu, S.; Tian, Z.; Zhang, L.; Hou, S.; Hu, S.; Wu, J.; Jing, Y.; Sun, H.; Yu, F.; Zhao, L.; Wang, R.; Tseng, H.R.; Zhau, H.E.; Chung, L.W.; Wu, K.; Wang, H.; Wu, J.B.; Nie, Y.; Shao, C. Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients. Oncotarget, 2016, 7(37), 59877-59891.
[49]
Detection of circulating cancer cells with von Hippel-Lindau gene mutation in peripheral blood of patients with renal cell carcinoma. Clin. Cancer Res., 2000, 6(10), 3817-3822.
[50]
Li, G.; Passebosc-Faure, K.; Gentil-Perret, A.; Lambert, C.; Genin, C.; Tostain, J. Cadherin-6 gene expression in conventional renal cell carcinoma: A useful marker to detect circulating tumor cells. Anticancer Res., 2005, 25, 377-381.
[51]
Goessl, C.; Müller, M.; Straub, B.; Miller, K. DNA alterations in body fluids as molecular tumor markers for urological malignancies. Eur. Urol., 2002, 41, 668-676.
[52]
Brisuda, A.; Pazourkova, E.; Soukup, V.; Horinek, A.; Hrbáček, J.; Capoun, O.; Svobodova, I.; Pospisilova, S.; Korabecna, M.; Mares, J.; Hanuš, T.; Babjuk, M. Urinary cell-free DNA quantification as non-invasive biomarker in patients with bladder cancer. Urol. Int., 2016, 96, 25-31.
[53]
Bryzgunova, O.E.; Laktionov, P.P. Extracellular nucleic acids in urine: Sources, structure, diagnostic potential. Acta Naturae, 2015, 7(3), 48-54.
[54]
Chen, L.; Cui, Z.; Liu, Y.; Bai, Y.; Lan, F. MicroRNAs as biomarkers for the diagnostics of bladder cancer: A meta-analysis. Clin. Lab., 2015, 61, 1101-1108.
[55]
Kinde, I.; Munari, E.; Faraj, S.F.; Hruban, R.H.; Schoenberg, M.; Bivalacqua, T.; Allaf, M.; Springer, S.; Wang, Y.; Diaz, L.A.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N.; Netto, G.J. TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. Cancer Res., 2013, 73, 7162-7167.
[56]
Hosen, I.; Rachakonda, P.S.; Heidenreich, B.; De Verdier, P.J.; Ryk, C.; Steineck, G.; Hemminki, K.; Kumar, R. Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer. Int. J. Cancer, 2015, 137, 1621-1629.
[57]
Beukers, W.; Van Der Keur, K.A.; Kandimalla, R.; Vergouwe, Y.; Steyerberg, E.W.; Boormans, J.L.; Jensen, J.B.; Lorente, J.A.; Real, F.X.; Segersten, U.; Orntoft, T.F.; Malats, N.; Malmström, P.U.; Dyrskjot, L.; Zwarthoff, E.C. FGFR3, TERT and OTX1 as a urinary biomarker combination for surveillance of patients with bladder cancer in a large prospective multicenter study. J. Urol., 2017, 197, 1410-1418.
[58]
Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9, 559.
[59]
Giulietti, M.; Occhipinti, G.; Principato, G.; Piva, F. Identification of candidate miRNA biomarkers for pancreatic ductal adenocarcinoma by weighted gene co-expression network analysis. Cell. Oncol., 2017, 40, 181-192.
[60]
Svetlovska, D.; Miskovska, V.; Cholujova, D.; Gronesova, P.; Cingelova, S.; Chovanec, M.; Sycova-Mila, Z.; Obertova, J.; Palacka, P.; Rajec, J.; Kalavska, K.; Usakova, V.; Luha, J.; Ondrus, D.; Spanik, S.; Mardiak, J.; Mego, M. Plasma cytokines correlated with disease characteristics, progression-free survival, and overall survival in testicular germ-cell tumor patients. Clin. Genitourin. Cancer, 2017, 15, 411-416.e2.
[61]
Syring, I.; Bartels, J.; Holdenrieder, S.; Kristiansen, G.; Müller, S.C.; Ellinger, J. Circulating Serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as biomarkers in patients with testicular germ cell cancer. J. Urol., 2015, 193, 331-337.
[62]
Spiekermann, M.; Belge, G.; Winter, N.; Ikogho, R.; Balks, T.; Bullerdiek, J.; Dieckmann, K.P. MicroRNA miR-371a-3p in serum of patients with germ cell tumours: Evaluations for establishing a serum biomarker. Andrology, 2015, 3, 78-84.
[63]
Dieckmann, K.P.; Spiekermann, M.; Balks, T.; Ikogho, R.; Anheuser, P.; Wosniok, W.; Loening, T.; Bullerdiek, J.; Belge, G. MicroRNA miR-371a-3p -A novel serum biomarker of testicular germ cell tumors: evidence for specificity from measurements in testicular vein blood and in neoplastic hydrocele fluid. Urol. Int., 2016, 97, 76-83.
[64]
IJzerman, M.J.; Berghuis, A.M.S.; De Bono, J.S.; Terstappen, L.W.M.M. Health economic impact of liquid biopsies in cancer management. Expert Rev. Pharmacoecon. Outcomes Res., 2018, 18(6), 593-599.
[65]
Tartari, F.; Santoni, M.; Burattini, L.; Mazzanti, P.; Onofri, A.; Berardi, R. Economic sustainability of anti-PD-1 agents nivolumab and pembrolizumab in cancer patients: Recent insights and future challenges. Cancer Treat. Rev., 2016, 48, 20-24.
[66]
Di Meo, A.; Saleeb, R.; Wala, S.J.; Khella, H.W.; Ding, Q.; Zhai, H.; Krishan, K.; Krizova, A.; Gabril, M.; Evans, A.; Brimo, F.; Pasic, M.D.; Finelli, A.; Diamandis, E.P.; Yousef, G.M. A miRNA-based classification of renal cell carcinoma subtypes by PCR and in situ hybridization. Oncotarget, 2018, 9(2), 2092-2104.
[67]
Zhang, D.Z.; Lau, K.M.; Chan, E.S.; Wang, G.; Szeto, C.C.; Wong, K.; Choy, R.K.; Ng, C.F. Cell-free urinary microRNA-99a and microRNA-125b are diagnostic markers for the non-invasive screening of bladder cancer. PLoS One, 2014, 9(7), e100793.
[68]
Daniel, R.; Wu, Q.; Williams, V.; Clark, G.; Guruli, G.; Zehner, Z. A Panel of microRNAs as diagnostic biomarkers for the identification of prostate cancer. Int. J. Mol. Sci., 2017, 18(6), 1281.
[69]
Tang, W.; Wan, S.; Yang, Z.; Teschendorff, A.E.; Zou, Q. Tumor origin detection with tissue-specific miRNA and DNA methylation markers. Bioinformatics, 2018, 34(3), 398-406.
[70]
Zeng, X.; Liu, L.; Lü, L.; Zou, Q. Prediction of potential disease-associated microRNAs using structural perturbation method. Bioinformatics, 2018, 34(14), 2425-2432.
[71]
Zeng, X.; Zhang, X.; Zou, Q. Integrative approaches for predicting microRNA function and prioritizing disease-related microRNA using biological interaction networks. Brief. Bioinform., 2016, 17(2), 193-203.
[72]
Ding, J.; Xing, Z.; Jiang, Z.; Chen, J.; Pan, L.; Qiu, J.; Xing, W. CT-based radiomic model predicts high grade of clear cell renal cell carcinoma. Eur. J. Radiol., 2018, 103, 51-56.
[73]
Tong, Y.; Udupa, J.K.; Wang, C.; Chen, J.; Venigalla, S.; Guzzo, T.J.; Mamtani, R.; Baumann, B.C.; Christodouleas, J.P.; Torigian, D.A. Radiomics-guided therapy for bladder cancer: Using an optimal biomarker approach to determine extent of bladder cancer invasion from t2-weighted magnetic resonance images. Adv. Radiat. Oncol., 2018, 3(3), 331-338.
[74]
Chaddad, A.; Niazi, T.; Probst, S.; Bladou, F.; Anidjar, M.; Bahoric, B. Predicting gleason score of prostate cancer patients using radiomic analysis. Front. Oncol., 2018, 8, 630.
[75]
Abdollahi, H.; Moid, B.; Shiri, I.; Razzaghdoust, A.; Saadipoor, A.; Mahdavi, A.; Galandooz, H.M.; Mahdavi, S.R. Machine learning-based radiomic models to predict intensity-modulated radiation therapy response, Gleason score and stage in prostate cancer. Radiol. Med., 2019.
[http://dx.doi.org/10.1007/s11547-018-0966-4]
[76]
Joice, G.A.; Rowe, S.P.; Gorin, M.A.; Pierorazio, P.M. Molecular Imaging for Evaluation of Viable Testicular Cancer Nodal Metastases. Curr. Urol. Rep., 2018, 19(12), 110.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy