Εmerging Biomarkers in the Diagnosis and Treatment of Testicular Tumors

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Abstract

Testicular germ cell tumors (TGCT) are the leading cause of cancer-related death in young males between the ages of 20-40. Surgical resection and cisplatin-based chemotherapy can achieve a cure for the majority of patients with TGCTs, with survival rates of up to 97% for patients diagnosed at an early stage. The use of serum biomarkers, such as AFP β-HCG, and LDH, plays a significant role in both diagnosis and evaluation of response to treatment, and despite their low sensitivity and specificity levels, they are an integral part of the current tumor staging system and daily practice. Molecular biomarkers, including micro-RNAs and gene-expression profiles, are currently being developed in TGCTs and could potentially hold a prominent place in the future diagnosis, treatment selection, surveillance, and prognostication of these tumors. This review discusses how current advances in our understanding of the underlying biology of TGCTs have helped biomarker discovery, with a focus on the recognition of key molecular alterations that could serve as potential indicators of disease onset, response to systemic or/and surgical therapies, and overall clinical course.

Graphical Abstract

[1]
Gilligan, T.; Lin, D.W.; Aggarwal, R.; Chism, D.; Cost, N.; Derweesh, I.H.; Emamekhoo, H.; Feldman, D.R.; Geynisman, D.M.; Hancock, S.L.; LaGrange, C.; Levine, E.G.; Longo, T.; Lowrance, W.; McGregor, B.; Monk, P.; Picus, J.; Pierorazio, P.; Rais-Bahrami, S.; Saylor, P.; Sircar, K.; Smith, D.C.; Tzou, K.; Vaena, D.; Vaughn, D.; Yamoah, K.; Yamzon, J.; Johnson-Chilla, A.; Keller, J.; Pluchino, L.A. Testicular Cancer, Version 2.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2019, 17(12), 1529-1554.
[http://dx.doi.org/10.6004/jnccn.2019.0058] [PMID: 31805523]
[2]
Znaor, A.; Lortet-Tieulent, J.; Jemal, A.; Bray, F. International variations and trends in testicular cancer incidence and mortality. Eur. Urol., 2014, 65(6), 1095-1106.
[http://dx.doi.org/10.1016/j.eururo.2013.11.004] [PMID: 24268506]
[3]
Nigam, M.; Aschebrook-Kilfoy, B.; Shikanov, S.; Eggener, S. Increasing incidence of testicular cancer in the United States and Europe between 1992 and 2009. World J. Urol., 2015, 33(5), 623-631.
[http://dx.doi.org/10.1007/s00345-014-1361-y] [PMID: 25030752]
[4]
Moch, H.; Cubilla, A.L.; Humphrey, P.A.; Reuter, V.E.; Ulbright, T.M. The 2016 WHO classification of tumours of the urinary system and male genital organs—part A: Renal, penile, and testicular tumours. Eur. Urol., 2016, 70(1), 93-105.
[http://dx.doi.org/10.1016/j.eururo.2016.02.029] [PMID: 26935559]
[5]
Oosterhuis, J.W.; Looijenga, L.H.J. Testicular germ-cell tumours in a broader perspective. Nat. Rev. Cancer, 2005, 5(3), 210-222.
[http://dx.doi.org/10.1038/nrc1568] [PMID: 15738984]
[6]
Dieckmann, K.P.; Simonsen-Richter, H.; Kulejewski, M.; Anheuser, P.; Zecha, H.; Isbarn, H.; Pichlmeier, U. Serum tumour markers in testicular germ cell tumours: Frequencies of elevated levels and extents of marker elevation are significantly associated with clinical parameters and with response to treatment. BioMed Res. Int., 2019, 2019, 5030349.
[http://dx.doi.org/10.1155/2019/5030349] [PMID: 31275973]
[7]
Batool, A.; Karimi, N.; Wu, X.N.; Chen, S.R.; Liu, Y.X. Testicular germ cell tumor: A comprehensive review. Cell. Mol. Life Sci., 2019, 76(9), 1713-1727.
[http://dx.doi.org/10.1007/s00018-019-03022-7] [PMID: 30671589]
[8]
Eyben, F.E. Laboratory markers and germ cell tumors. Crit. Rev. Clin. Lab. Sci., 2003, 40(4), 377-427.
[http://dx.doi.org/10.1080/10408360390247814] [PMID: 14582602]
[9]
Oosterhuis, J.W.; Looijenga, L.H.J. Human germ cell tumours from a developmental perspective. Nat. Rev. Cancer, 2019, 19(9), 522-537.
[http://dx.doi.org/10.1038/s41568-019-0178-9] [PMID: 31413324]
[10]
Skakkebæk, N.E.; Berthelsen, J.G.; Giwercman, A.; Müller, J. Carcinoma-in-situ of the testis: Possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int. J. Androl., 1987, 10(1), 19-28.
[http://dx.doi.org/10.1111/j.1365-2605.1987.tb00161.x] [PMID: 3034791]
[11]
Honecker, F.; Stoop, H.; Mayer, F.; Bokemeyer, C.; Castrillon, D.H.; Lau, Y.F.C.; Looijenga, L.H.J.; Oosterhuis, J.W. Germ cell lineage differentiation in non-seminomatous germ cell tumours. J. Pathol., 2006, 208(3), 395-400.
[http://dx.doi.org/10.1002/path.1872] [PMID: 16273510]
[12]
Ottesen, A.M.; Skakkebaek, N.E.; Lundsteen, C.; Leffers, H.; Larsen, J.; Rajpert-De Meyts, E. High-resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor development. Genes Chromosomes Cancer, 2003, 38(2), 117-125.
[http://dx.doi.org/10.1002/gcc.10244] [PMID: 12939739]
[13]
Rodriguez, S.; Jafer, O.; Goker, H.; Summersgill, B.M.; Zafarana, G.; Gillis, A.J.M.; van Gurp, R.J.H.L.M.; Oosterhuis, J.W.; Lu, YJ.; Huddart, R.; Cooper, C.S.; Clark, J.; Looijenga, L.H.J.; Shipley, J.M. Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1. Oncogene, 2003, 22(12), 1880-1891.
[http://dx.doi.org/10.1038/sj.onc.1206302] [PMID: 12660824]
[14]
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.; Akbani, R.; Wheeler, D.A.; Laird, P.W.; Nathanson, K.L.; Cortessis, V.K.; Hoadley, K.A.; Wang, L.; Xi, L.; Wheeler, D.; Hughes, D.; Covington, K.; Jayaseelan, J.C.; Korchina, V.; Lewis, L.; Hu, J.; Doddapaneni, H.V.; Muzny, D.; Gibbs, R.; Hoadley, K.A.; Hollern, D.; Vincent, B.G.; Chai, S.; Smith, C.C.; Auman, J.T.; Shi, Y.; Meng, S.; Skelly, T.; Tan, D.; Veluvolu, U.; Mieczkowski, P.A.; Jones, C.D.; Wilkerson, M.D.; Balu, S.; Bodenheimer, T.; Hoyle, A.P.; Jefferys, S.R.; Mose, L.E.; Simons, J.V.; Soloway, M.G.; Roach, J.; Parker, J.S.; Hayes, D.N.; Perou, C.M.; Shih, J.; Cherniack, A.D.; Meyerson, M.; Saksena, G.; Cibulskis, C.; Schumacher, S.E.; Beroukhim, R.; Gabriel, S.B.; Bowlby, R.; Mungall, A.J.; Brooks, D.; Kasaian, K.; Ally, A.; Balasundaram, M.; Carlsen, R.; Cheung, D.; Chuah, E.; Dhalla, N.; Holt, R.A.; Jones, S.J.M.; Ma, Y.; Mayo, M.; Moore, R.A.; Robertson, A.G.; Schein, J.E.; Sipahimalani, P.; Tam, A.; Thiessen, N.; Wong, T.; Marra, M.A.; Shen, H.; Zhou, W.; Laird, P.W.; Weisenberger, D.J.; Van Den Berg, D.J.; Lai, P.H.; Berrios, M.; Holbrook, A.; Bootwalla, M.S.; Maglinte, D.T.; Armenia, J.; Sánchez-Vega, F.; Schultz, N.; Chakravarty, D.; Gao, J.; Heins, Z.; Kundra, R.; Ochoa, A.; Liu, M.; Sander, C.; Ladanyi, M.; Thorsson, V.; Radenbaugh, A.J.; Newton, Y.; Stuart, J.M.; Cho, J.; Heiman, D.I.; Noble, M.S.; Zhang, H.; Getz, G.; Gehlenborg, N.; Saksena, G.; Voet, D.; Lin, P.; Frazer, S.; Kim, J.; Lawrence, M.S.; Meier, S.; Defreitas, T.; Chin, L.; Hegde, A.M.; Akbani, R.; Weinstein, J.N.; Liu, W.; Mills, G.B.; Lu, Y.; Pyle, L.C.; Pluta, J.; Nathanson, K.L.; Tickoo, S.K.; Reuter, V.E.; Mehra, R.; Looijenga, L.; Bryce, A.H.; Cárcano, F.M.; Carvalho, A.L.; Cortessis, V.K.; Feldman, D.; Godoy, G.; Ittmann, M.; Jones, J.; Kulis, T.; Lerner, S.; Lessel, D.; Nathanson, K.L.; Shelley, C.S.; Vidal, D.O.; Leraas, K.M.; Lichtenberg, T.M.; Bowen, J.; Gastier-Foster, J.M.; Gerken, M.; Helsel, C.; Ramirez, N.C.; Wise, L.; Zmuda, E.; Cottingham, S.; Chesla, D.; Saller, C.; Tarvin, K.; Lopes, L.F.; Scapulatempo-Neto, C.; Aredes, N.D.A.; Oosterhuis, W.; Gillis, A.; Stoop, H.; Eijkenboom, W.; Sandusky, G.; Martin, S.E.; Aron, M.; Daneshmand, S.; Djaladat, H.; Quinn, D.; Dorff, T.; Lennerz, J.K.; Thorne, L.B.; Gamulin, M.; Kastelan, Z.; Hudolin, T.; Kubisch, C.; Boice, L.; Huang, M.; Perou, A.H.; Rathmell, W.K.; Pihl, T.; Wan, Y.; Sun, Q.; Naresh, R.; Chudamani, S.; Liu, J.; Lolla, L.; Wu, Y.; Ferguson, M.L.; Zenklusen, J.C.; Felau, I.; Zhang, J.J.; Sheth, M.; Demchok, J.A.; Yang, L.; Wang, Z.; Tarnuzzer, R.; Hutter, C.M.; Sofia, H.J.; Davidsen, T.M. Integrated molecular characterization of testicular germ cell tumors. Cell Rep., 2018, 23(11), 3392-3406.
[http://dx.doi.org/10.1016/j.celrep.2018.05.039] [PMID: 29898407]
[15]
Litchfield, K.; Levy, M.; Huddart, R.A.; Shipley, J.; Turnbull, C. The genomic landscape of testicular germ cell tumours: from susceptibility to treatment. Nat. Rev. Urol., 2016, 13(7), 409-419.
[http://dx.doi.org/10.1038/nrurol.2016.107] [PMID: 27296647]
[16]
Urbini, M.; Schepisi, G.; Bleve, S.; Virga, A.; Gianni, C.; Gurioli, G.; Ulivi, P.; De Giorgi, U. Primary mediastinal and testicular germ cell tumors in adolescents and adults: A comparison of genomic alterations and clinical implications. Cancers (Basel), 2021, 13(20), 5223.
[http://dx.doi.org/10.3390/cancers13205223] [PMID: 34680371]
[17]
Necchi, A.; Bratslavsky, G.; Chung, J.; Millis, S.; Gay, L.M.; Ali, S.M.; Ross, J.S. Genomic features for therapeutic insights of chemotherapy-resistant, primary mediastinal nonseminomatous germ cell tumors and comparison with gonadal counterpart. Oncologist, 2019, 24(4), e142-e145.
[http://dx.doi.org/10.1634/theoncologist.2018-0430] [PMID: 30659078]
[18]
Li, X.; Su, Y.; Zhang, J.; Zhu, Y.; Xu, Y.; Wu, G. LAPTM5 Plays a key role in the diagnosis and prognosis of testicular germ cell tumors. Int. J. Genomics, 2021, 2021, 1-18.
[http://dx.doi.org/10.1155/2021/8816456] [PMID: 33521125]
[19]
Kulis, M.; Esteller, M. DNA methylation and cancer. Adv. Genet., 2010, 70, 27-56.
[http://dx.doi.org/10.1016/B978-0-12-380866-0.60002-2] [PMID: 20920744]
[20]
Yu, X.; Han, Y.; Liu, S.; Jiang, W.; Song, Y.; Tong, J.; Qiao, T.; Lv, Z.; Li, D. Analysis of genetic alterations related to DNA methylation in testicular germ cell tumors based on data mining. Cytogenet. Genome Res., 2021, 161(6-7), 382-394.
[http://dx.doi.org/10.1159/000516385] [PMID: 34433169]
[21]
Mandelbaum, J.; Bhagat, G.; Tang, H.; Mo, T.; Brahmachary, M.; Shen, Q.; Chadburn, A.; Rajewsky, K.; Tarakhovsky, A.; Pasqualucci, L.; Dalla-Favera, R. BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. Cancer Cell, 2010, 18(6), 568-579.
[http://dx.doi.org/10.1016/j.ccr.2010.10.030] [PMID: 21156281]
[22]
Liu, Y.; Huang, D.; Wang, Z.; Wu, C.; Zhang, Z.; Wang, D.; Li, Z.; Zhu, T.; Yang, S.; Sun, W. LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer. Sci. Rep., 2016, 6(1), 36050.
[http://dx.doi.org/10.1038/srep36050] [PMID: 27779255]
[23]
Kizil, C.; Küchler, B.; Yan, J.J.; Özhan, G.; Moro, E.; Argenton, F.; Brand, M.; Weidinger, G.; Antos, C.L. Simplet/Fam53b is required for Wnt signal transduction by regulating β-catenin nuclear localization. Development, 2014, 141(18), 3529-3539.
[http://dx.doi.org/10.1242/dev.108415] [PMID: 25183871]
[24]
Looijenga, L.H.J.; Stoop, H.; Biermann, K. Testicular cancer: Biology and biomarkers. Virchows Arch., 2014, 464(3), 301-313.
[http://dx.doi.org/10.1007/s00428-013-1522-1] [PMID: 24487784]
[25]
de Jong, J.; Stoop, H.; Gillis, A.J.M.; van Gurp, R.J.H.L.M.; van de Geijn, G-J.M.; Boer, M.; Hersmus, R.; Saunders, P.T.K.; Anderson, R.A.; Oosterhuis, J.W.; Looijenga, L.H.J. Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications. J. Pathol., 2008, 215(1), 21-30.
[http://dx.doi.org/10.1002/path.2332] [PMID: 18348160]
[26]
Nettersheim, D.; Heimsoeth, A.; Jostes, S.; Schneider, S.; Fellermeyer, M.; Hofmann, A.; Schorle, H. SOX2 is essential for in vivo reprogramming of seminoma-like TCam-2 cells to an embryonal carcinoma-like fate. Oncotarget, 2016, 7(30), 47095-47110.
[http://dx.doi.org/10.18632/oncotarget.9903] [PMID: 27283990]
[27]
Jostes, S.V.; Fellermeyer, M.; Arévalo, L.; Merges, G.E.; Kristiansen, G.; Nettersheim, D.; Schorle, H. Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate. Int. J. Cancer, 2020, 146(6), 1592-1605.
[http://dx.doi.org/10.1002/ijc.32714] [PMID: 31583686]
[28]
Rudolph, C.; Melau, C.; Nielsen, J.E.; Vile Jensen, K.; Liu, D.; Pena-Diaz, J.; Rajpert-De Meyts, E.; Rasmussen, L.J.; Jørgensen, A. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours. Cell Oncol., 2017, 40(4), 341-355.
[http://dx.doi.org/10.1007/s13402-017-0326-8] [PMID: 28536927]
[29]
Velasco, A.; Corvalan, A.; Wistuba, I.I.; Riquelme, E.; Chuaqui, R.; Majerson, A.; Leach, F.S. Mismatch repair expression in testicular cancer predicts recurrence and survival. Int. J. Cancer, 2008, 122(8), 1774-1777.
[http://dx.doi.org/10.1002/ijc.23291] [PMID: 18076065]
[30]
Damjanov, I. Testicular germ cell tumors: Serological and immunohistochemical diagnosis. Acta Med. Acad., 2021, 50(1), 58-70.
[http://dx.doi.org/10.5644/ama2006-124.326] [PMID: 34075764]
[31]
Tomasi, T.B., Jr Structure and function of alpha-fetoprotein. Annu. Rev. Med., 1977, 28(1), 453-465.
[http://dx.doi.org/10.1146/annurev.me.28.020177.002321] [PMID: 67821]
[32]
Damjanov, I.; Amenta, P.S.; Zarghami, F. Transformation of an AFP‐positive yolk sac carcinoma into an AFP‐negative neoplasm: Evidence for in vivo cloning of the human parietal yolk sac carcinoma. Cancer, 1984, 53(9), 1902-1907.
[http://dx.doi.org/10.1002/1097-0142(19840501)53:9<1902::AID-CNCR2820530916>3.0.CO;2-#] [PMID: 6200199]
[33]
Cole, L.A. Human chorionic gonadotropin and associated molecules. Expert Rev. Mol. Diagn., 2009, 9(1), 51-73.
[http://dx.doi.org/10.1586/14737159.9.1.51] [PMID: 19099349]
[34]
Gilligan, T.D.; Seidenfeld, J.; Basch, E.M.; Einhorn, L.H.; Fancher, T.; Smith, D.C.; Stephenson, A.J.; Vaughn, D.J.; Cosby, R.; Hayes, D.F. American Society of Clinical Oncology. American Society of Clinical oncology clinical practice guideline on uses of serum tumor markers in adult males with germ cell tumors. J. Clin. Oncol., 2010, 28(20), 3388-3404.
[http://dx.doi.org/10.1200/JCO.2009.26.4481] [PMID: 20530278]
[35]
Leão, R.; Ahmad, A.E.; Hamilton, R.J. Testicular cancer biomarkers: A role for precision medicine in testicular cancer. Clin. Genitourin. Cancer, 2019, 17(1), e176-e183.
[http://dx.doi.org/10.1016/j.clgc.2018.10.007] [PMID: 30497810]
[36]
di Pietro, A.; Vries, E.G.E.; Gietema, J.A.; Spierings, D.C.J.; de Jong, S. Testicular germ cell tumours: The paradigm of chemo-sensitive solid tumours. Int. J. Biochem. Cell Biol., 2005, 37(12), 2437-2456.
[http://dx.doi.org/10.1016/j.biocel.2005.06.014] [PMID: 16099193]
[37]
Lobo, J.; Jerónimo, C.; Henrique, R. Cisplatin resistance in testicular germ cell tumors: Current challenges from various perspectives. Cancers, 2020, 12(6), 1601.
[http://dx.doi.org/10.3390/cancers12061601] [PMID: 32560427]
[38]
Einhorn, L.H.; Williams, S.D.; Chamness, A.; Brames, M.J.; Perkins, S.M.; Abonour, R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N. Engl. J. Med., 2007, 357(4), 340-348.
[http://dx.doi.org/10.1056/NEJMoa067749] [PMID: 17652649]
[39]
Feldman, D.R.; Bosl, G.J.; Sheinfeld, J.; Motzer, R.J. Medical treatment of advanced testicular cancer. JAMA, 2008, 299(6), 672-684.
[http://dx.doi.org/10.1001/jama.299.6.672] [PMID: 18270356]
[40]
International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J. Clin. Oncol., 1997, 15(2), 594-603.
[http://dx.doi.org/10.1200/JCO.1997.15.2.594] [PMID: 9053482]
[41]
Szymendera, J.J.; Zborzil, J.; Sikorowa, L.; Leńko, J.; Kamińska, J.A.; Gadek, A. Evaluation of five tumor markers (AFP, CEA, hCG, hPL and SP1) in monitoring therapy and follow-up of patients with testicular germ cell tumors. Oncology, 1983, 40(1), 1-10.
[http://dx.doi.org/10.1159/000225681] [PMID: 6185897]
[42]
Klepp, O.; Flodgren, P.; Maartman-Moe, H.; Lindholm, C.E.; Unsgaard, B.; Teigum, H.; Fosså, S.D.; Paus, E. Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Ann. Oncol., 1990, 1(4), 281-288.
[http://dx.doi.org/10.1093/oxfordjournals.annonc.a057749] [PMID: 1702312]
[43]
Pehserl, A.M.; Ress, A.; Stanzer, S.; Resel, M.; Karbiener, M.; Stadelmeyer, E.; Stiegelbauer, V.; Gerger, A.; Mayr, C.; Scheideler, M.; Hutterer, G.; Bauernhofer, T.; Kiesslich, T.; Pichler, M. Comprehensive analysis of mirnome alterations in response to sorafenib treatment in colorectal cancer cells. Int. J. Mol. Sci., 2016, 17(12), 2011.
[http://dx.doi.org/10.3390/ijms17122011] [PMID: 27916938]
[44]
Smolle, M.A.; Prinz, F.; Calin, G.A.; Pichler, M. Current concepts of non-coding RNA regulation of immune checkpoints in cancer. Mol. Aspects Med., 2019, 70, 117-126.
[http://dx.doi.org/10.1016/j.mam.2019.09.007] [PMID: 31582259]
[45]
Turchinovich, A.; Samatov, T.R.; Tonevitsky, A.G.; Burwinkel, B. Circulating miRNAs: Cell–cell communication function? Front. Genet., 2013, 4, 119.
[http://dx.doi.org/10.3389/fgene.2013.00119] [PMID: 23825476]
[46]
Zhao, X.Y.; Gao, Y.L.; Li, D.F.; Liu, H.C.; Zhu, R.F.; Zhu, C.T. Diagnostic performance of microRNAs in testicular germ cell tumors: A systematic review and meta-analysis. Aging (Albany NY), 2021, 13(15), 19657-19677.
[http://dx.doi.org/10.18632/aging.203376] [PMID: 34343969]
[47]
Kuo, C.H.; Deng, J.H.; Deng, Q.; Ying, S.Y. A novel role of miR-302/367 in reprogramming. Biochem. Biophys. Res. Commun., 2012, 417(1), 11-16.
[http://dx.doi.org/10.1016/j.bbrc.2011.11.058] [PMID: 22138244]
[48]
Lee, J.; Go, Y.; Kang, I.; Han, Y.M.; Kim, J. Oct-4 controls cell-cycle progression of embryonic stem cells. Biochem. J., 2010, 426(2), 171-181.
[http://dx.doi.org/10.1042/BJ20091439] [PMID: 19968627]
[49]
Murray, M.J.; Halsall, D.J.; Hook, C.E.; Williams, D.M.; Nicholson, J.C.; Coleman, N. Identification of microRNAs From the miR-371~373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am. J. Clin. Pathol., 2011, 135(1), 119-125.
[http://dx.doi.org/10.1309/AJCPOE11KEYZCJHT] [PMID: 21173133]
[50]
Das, M.K.; Evensen, H.S.F.; Furu, K.; Haugen, T.B. miRNA-302s may act as oncogenes in human testicular germ cell tumours. Sci. Rep., 2019, 9(1), 9189.
[http://dx.doi.org/10.1038/s41598-019-45573-6] [PMID: 31235829]
[51]
Suh, M.R.; Lee, Y.; Kim, J.Y.; Kim, S.K.; Moon, S.H.; Lee, J.Y.; Cha, K.Y.; Chung, H.M.; Yoon, H.S.; Moon, S.Y.; Kim, V.N.; Kim, K.S. Human embryonic stem cells express a unique set of microRNAs. Dev. Biol., 2004, 270(2), 488-498.
[http://dx.doi.org/10.1016/j.ydbio.2004.02.019] [PMID: 15183728]
[52]
Voorhoeve, P.M.; le Sage, C.; Schrier, M.; Gillis, A.J.M.; Stoop, H.; Nagel, R.; Liu, Y.P.; van Duijse, J.; Drost, J.; Griekspoor, A.; Zlotorynski, E.; Yabuta, N.; De Vita, G.; Nojima, H.; Looijenga, L.H.J.; Agami, R. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell, 2006, 124(6), 1169-1181.
[http://dx.doi.org/10.1016/j.cell.2006.02.037] [PMID: 16564011]
[53]
Wei, F.; Cao, C.; Xu, X.; Wang, J. Diverse functions of miR-373 in cancer. J. Transl. Med., 2015, 13(1), 162.
[http://dx.doi.org/10.1186/s12967-015-0523-z] [PMID: 25990556]
[54]
Zhou, A-D.; Diao, L-T.; Xu, H.; Xiao, Z-D.; Li, J-H.; Zhou, H.; Qu, L-H. β-Catenin/LEF1 transactivates the microRNA-371-373 cluster that modulates the Wnt/β-catenin-signaling pathway. Oncogene, 2012, 31(24), 2968-2978.
[http://dx.doi.org/10.1038/onc.2011.461] [PMID: 22020335]
[55]
Dieckmann, K.P.; Radtke, A.; Geczi, L.; Matthies, C.; Anheuser, P.; Eckardt, U.; Sommer, J.; Zengerling, F.; Trenti, E.; Pichler, R.; Belz, H.; Zastrow, S.; Winter, A.; Melchior, S.; Hammel, J.; Kranz, J.; Bolten, M.; Krege, S.; Haben, B.; Loidl, W.; Ruf, C.G.; Heinzelbecker, J.; Heidenreich, A.; Cremers, J.F.; Oing, C.; Hermanns, T.; Fankhauser, C.D.; Gillessen, S.; Reichegger, H.; Cathomas, R.; Pichler, M.; Hentrich, M.; Eredics, K.; Lorch, A.; Wülfing, C.; Peine, S.; Wosniok, W.; Bokemeyer, C.; Belge, G. Serum levels of MicroRNA-371a-3p (M371 Test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J. Clin. Oncol., 2019, 37(16), 1412-1423.
[http://dx.doi.org/10.1200/JCO.18.01480] [PMID: 30875280]
[56]
Vilela-Salgueiro, B.; Barros-Silva, D.; Lobo, J.; Costa, A.L.; Guimarães, R.; Cantante, M.; Lopes, P.; Braga, I.; Oliveira, J.; Henrique, R.; Jerónimo, C. Germ cell tumour subtypes display differential expression of microRNA371a-3p. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2018, 373(1748), 20170338.
[http://dx.doi.org/10.1098/rstb.2017.0338] [PMID: 29685967]
[57]
Li, J.; Guo, Y.; Liang, X.; Sun, M.; Wang, G.; De, W.; Wu, W. MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4. J. Cancer Res. Clin. Oncol., 2012, 138(5), 763-774.
[http://dx.doi.org/10.1007/s00432-012-1154-x] [PMID: 22270966]
[58]
Kurashige, J.; Watanabe, M.; Iwatsuki, M.; Kinoshita, K.; Saito, S.; Hiyoshi, Y.; Kamohara, H.; Baba, Y.; Mimori, K.; Baba, H. Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. Br. J. Cancer, 2012, 106(1), 182-188.
[http://dx.doi.org/10.1038/bjc.2011.509] [PMID: 22108521]
[59]
Mavrakis, K.J.; Van Der Meulen, J.; Wolfe, A.L.; Liu, X.; Mets, E.; Taghon, T.; Khan, A.A.; Setty, M.; Rondou, P.; Vandenberghe, P.; Delabesse, E.; Benoit, Y.; Socci, N.B.; Leslie, C.S.; Van Vlierberghe, P.; Speleman, F.; Wendel, H.G. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat. Genet., 2011, 43(7), 673-678.
[http://dx.doi.org/10.1038/ng.858] [PMID: 21642990]
[60]
Kurozumi, A.; Goto, Y.; Matsushita, R.; Fukumoto, I.; Kato, M.; Nishikawa, R.; Sakamoto, S.; Enokida, H.; Nakagawa, M.; Ichikawa, T.; Seki, N. Tumor‐suppressive micro RNA ‐223 inhibits cancer cell migration and invasion by targetingITGA 3/ITGB 1 signaling in prostate cancer. Cancer Sci., 2016, 107(1), 84-94.
[http://dx.doi.org/10.1111/cas.12842] [PMID: 26509963]
[61]
Liu, J.; Shi, H.; Li, X.; Chen, G.; Larsson, C.; Lui, W.O. miR-223-3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors. Int. J. Oncol., 2017, 50(2), 356-364.
[http://dx.doi.org/10.3892/ijo.2016.3807] [PMID: 28000896]
[62]
Flor, I.; Spiekermann, M.; Löning, T.; Dieckmann, K.P.; Belge, G.; Bullerdiek, J. Expression of microRNAs of C19MC in different histological types of testicular germ cell tumour. Cancer Genom. Proteom., 2016, 13(4), 281-289.
[PMID: 27365378]
[63]
Yuan, S.; Tang, C.; Zhang, Y.; Wu, J.; Bao, J.; Zheng, H.; Xu, C.; Yan, W. mir-34b/c and mir-449a/b/c are required for spermatogenesis, but not for the first cleavage division in mice. Biol. Open, 2015, 4(2), 212-223.
[http://dx.doi.org/10.1242/bio.201410959] [PMID: 25617420]
[64]
Yang, X.; Feng, M.; Jiang, X.; Wu, Z.; Li, Z.; Aau, M.; Yu, Q. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb–E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev., 2009, 23(20), 2388-2393.
[http://dx.doi.org/10.1101/gad.1819009] [PMID: 19833767]
[65]
Yong-Ming, H.; Ai-Jun, J.; Xiao-Yue, X.; Jian-Wei, L.; Chen, Y.; Ye, C. miR-449a. Anticancer Drugs, 2017, 28(10), 1067-1078.
[http://dx.doi.org/10.1097/CAD.0000000000000555] [PMID: 29023247]
[66]
Lian, J.; Tian, H.; Liu, L.; Zhang, X-S.; Li, W-Q.; Deng, Y-M.; Yao, G-D.; Yin, M-M.; Sun, F. Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1. Cell Death Dis., 2010, 1(11), e94.
[http://dx.doi.org/10.1038/cddis.2010.70] [PMID: 21368870]
[67]
Alsamman, K.; El-Masry, O.S. Interferon regulatory factor 1 inactivation in human cancer. Biosci. Rep., 2018, 38(3), BSR20171672.
[http://dx.doi.org/10.1042/BSR20171672] [PMID: 29599126]
[68]
Huang, H.; Tian, H.; Duan, Z.; Cao, Y.; Zhang, X.S.; Sun, F. microRNA-383 impairs phosphorylation of H2AX by targeting PNUTS and inducing cell cycle arrest in testicular embryonal carcinoma cells. Cell. Signal., 2014, 26(5), 903-911.
[http://dx.doi.org/10.1016/j.cellsig.2014.01.016] [PMID: 24462707]
[69]
De Martino, M.; Esposito, F.; Chieffi, P. An update on microRNAs as potential novel therapeutic targets in testicular germ cell tumors. Intractable Rare Dis. Res., 2020, 9(3), 184-186.
[http://dx.doi.org/10.5582/irdr.2020.03025] [PMID: 32844079]
[70]
De Martino, M.; Esposito, F.; Pellecchia, S.; Cortez Cardoso Penha, R.; Botti, G.; Fusco, A.; Chieffi, P. HMGA1-regulating microRNAs Let-7a and miR-26a are downregulated in human seminomas. Int. J. Mol. Sci., 2020, 21(8), 3014.
[http://dx.doi.org/10.3390/ijms21083014] [PMID: 32344629]
[71]
Chieffi, P.; Battista, S.; Barchi, M.; Di Agostino, S.; Pierantoni, G.M.; Fedele, M.; Chiariotti, L.; Tramontano, D.; Fusco, A. HMGA1 and HMGA2 protein expression in mouse spermatogenesis. Oncogene, 2002, 21(22), 3644-3650.
[http://dx.doi.org/10.1038/sj.onc.1205501] [PMID: 12032866]
[72]
Rosas Plaza, X.; van Agthoven, T.; Meijer, C.; van Vugt, M.A.T.M.; de Jong, S.; Gietema, J.A.; Looijenga, L.H.J. miR-371a-3p, miR-373-3p and miR-367-3p as serum biomarkers in metastatic testicular germ cell cancers before, during and after chemotherapy. Cells, 2019, 8(10), 1221.
[http://dx.doi.org/10.3390/cells8101221] [PMID: 31597402]
[73]
Terbuch, A.; Adiprasito, J.; Stiegelbauer, V.; Seles, M.; Klec, C.; Pichler, G.; Resel, M.; Posch, F.; Lembeck, A.; Stöger, H.; Szkandera, J.; Pummer, K.; Bauernhofer, T.; Hutterer, G.; Gerger, A.; Stotz, M.; Pichler, M. MiR-371a-3p serum levels are increased in recurrence of testicular germ cell tumor patients. Int. J. Mol. Sci., 2018, 19(10), 3130.
[http://dx.doi.org/10.3390/ijms19103130] [PMID: 30321995]
[74]
Kremer, L.; von Brandenstein, M.; Wittersheim, M.; Koeditz, B.; Paffenholz, P.; Hellmich, M.; Pfister, D.; Heidenreich, A.; Nestler, T. The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens. Transl. Androl. Urol., 2021, 10(4), 1647-1655.
[http://dx.doi.org/10.21037/tau-20-1349] [PMID: 33968653]
[75]
Regouc, M.; Belge, G.; Lorch, A.; Dieckmann, K.P.; Pichler, M. Non-Coding microRNAs as novel potential tumor markers in testicular cancer. Cancers, 2020, 12(3), 749.
[http://dx.doi.org/10.3390/cancers12030749] [PMID: 32235691]
[76]
Fankhauser, C.D.; Curioni-Fontecedro, A.; Allmann, V.; Beyer, J.; Tischler, V.; Sulser, T.; Moch, H.; Bode, P.K. Frequent PD-L1 expression in testicular germ cell tumors. Br. J. Cancer, 2015, 113(3), 411-413.
[http://dx.doi.org/10.1038/bjc.2015.244] [PMID: 26171934]
[77]
Pęksa, R.; Kunc, M.; Popęda, M.; Piątek, M.; Bieńkowski, M.; Żok, J.; Starzyńska, A.; Perdyan, A.; Sowa, M.; Duchnowska, R.; Biernat, W. Combined assessment of immune checkpoint regulator VISTA on tumor-associated immune cells and platelet-to-lymphocyte ratio identifies advanced germ cell tumors with higher risk of unfavorable outcomes. Cancers, 2021, 13(8), 1750.
[http://dx.doi.org/10.3390/cancers13081750] [PMID: 33916925]
[78]
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(1), 209-214.
[http://dx.doi.org/10.1093/annonc/mdx680] [PMID: 29045540]
[79]
Roška, J.; Wachsmannová, L.; Hurbanová, L.; Šestáková, Z.; Mueller, T.; Jurkovičová, D.; Chovanec, M. Differential gene expression in cisplatin-resistant and -sensitive testicular germ cell tumor cell lines. Oncotarget, 2020, 11(51), 4735-4753.
[http://dx.doi.org/10.18632/oncotarget.27844] [PMID: 33473258]