{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T09:30:33Z","timestamp":1777109433665,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T00:00:00Z","timestamp":1502841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series. Thus far, it appears PeCa has diverse mechanisms of carcinogenesis affecting similar molecular pathways. In this review, we evaluate the current landscape of the molecular carcinogenesis of PeCa and explore ongoing research on potential actionable targets of therapy. The emergence of anti-epidermal growth factor receptor (EGFR) and other immunotherapeutic strategies may improve outcomes for PeCa patients.<\/jats:p>","DOI":"10.3390\/ijms18081777","type":"journal-article","created":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T10:43:51Z","timestamp":1502880231000},"page":"1777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Advances in Understanding of Penile Carcinogenesis: The Search for Actionable Targets"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-0382","authenticated-orcid":false,"given":"Juan","family":"Chipollini","sequence":"first","affiliation":[{"name":"Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Chaing","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mounsif","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Kidd","sequence":"additional","affiliation":[{"name":"Department of Urology, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, South Bend, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Spiess","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/cncr.20519","article-title":"Squamous cell carcinoma of the penis: Evaluation of data from the surveillance, epidemiology, and end results program","volume":"101","author":"Rippentrop","year":"2004","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.urolonc.2006.08.029","article-title":"Incidence trends in primary malignant penile cancer","volume":"25","author":"Maldonado","year":"2007","journal-title":"Urol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.eururo.2010.01.039","article-title":"EAU penile cancer guidelines 2009","volume":"57","author":"Pizzocaro","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ucl.2016.06.003","article-title":"The Role of Human Papilloma Virus in Penile Carcinogenesis and Preneoplastic Lesions: A Potential Target for Vaccination and Treatment Strategies","volume":"43","author":"Diorio","year":"2016","journal-title":"Urol. Clin. North Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.ucl.2016.06.009","article-title":"Emerging Systemic Therapies for the Management of Penile Cancer","volume":"43","author":"Gupta","year":"2016","journal-title":"Urol. Clin North Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"594","DOI":"10.6004\/jnccn.2013.0075","article-title":"Penile cancer: Clinical Practice Guidelines in Oncology","volume":"11","author":"Clark","year":"2013","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1479-5876-11-161","article-title":"Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: A retropective study","volume":"11","author":"Perdona","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.eururo.2014.10.017","article-title":"EAU guidelines on penile cancer: 2014 update","volume":"67","author":"Hakenberg","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/jso.20170","article-title":"Contemporary management of penile squamous cell carcinoma","volume":"89","author":"Kroon","year":"2005","journal-title":"J. Surg. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.eururo.2008.04.016","article-title":"Recurrence patterns of squamous cell carcinoma of the penis: Recommendations for follow-up based on a two-centre analysis of 700 patients","volume":"54","author":"Leijte","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Van Poppel, H., Watkin, N.A., Osanto, S., Moonen, L., Horwich, A., Kataja, V., and Group, E.G.W. (2013). Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol.","DOI":"10.1093\/annonc\/mdt286"},{"key":"ref_12","first-page":"153","article-title":"pT1 penile squamous cell carcinoma: A clinicopathologic study of 56 cases treated by CO2 laser therapy","volume":"31","author":"Colecchia","year":"2009","journal-title":"Anal. Quant. Cytol. Histol."},{"key":"ref_13","unstructured":"(2017, July 31). Penile Cancer. Available online: http:\/\/www.tri-kobe.org\/nccn\/guideline\/urological\/english\/penile.pdf."},{"key":"ref_14","unstructured":"(2017, July 31). InPACT. Available online: http:\/\/www.icr.ac.uk\/our-research\/our-research-centres\/clinical-trials-and-statistics-unit\/clinical-trials\/inpact."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1200\/JCO.2010.29.5477","article-title":"Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: A phase II study","volume":"28","author":"Pagliaro","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Di Lorenzo, G., Buonerba, C., Federico, P., Perdon\u00e0, S., Aieta, M., Rescigno, P., D\u2019Aniello, C., Puglia, L., Petremolo, A., and Ferro, M. (2012). Cisplatin and 5-fluorouracil in inoperable, stage IV squamous cell carcinoma of the penis. BJU Int.","DOI":"10.1111\/j.1464-410X.2012.11453.x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.eururo.2008.07.014","article-title":"Taxanes in combination with cisplatin and fluorouracil for advanced penile cancer: Preliminary results","volume":"55","author":"Pizzocaro","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/S0022-5347(05)68815-5","article-title":"Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: A Southwest Oncology Group study","volume":"161","author":"Haas","year":"1999","journal-title":"J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/0090-4295(93)90273-D","article-title":"Penile cancer chemotherapy: Twelve years\u2019 experience at Institut Gustave-Roussy","volume":"42","author":"Kattan","year":"1993","journal-title":"Urology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0022-5347(01)62402-9","article-title":"Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: A phase II study of methotrexate, cisplatin and bleomycin","volume":"160","author":"Corral","year":"1998","journal-title":"J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.eururo.2011.08.028","article-title":"Paclitaxel in pretreated metastatic penile cancer: Final results of a phase 2 study","volume":"60","author":"Federico","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00345-008-0302-z","article-title":"Penile cancer: Epidemiology, pathogenesis and prevention","volume":"27","author":"Bleeker","year":"2009","journal-title":"World J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53.e1","DOI":"10.1016\/j.urolonc.2013.08.010","article-title":"Implications for human papillomavirus in penile cancer","volume":"32","author":"Flaherty","year":"2014","journal-title":"Urol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3322\/caac.21354","article-title":"Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies","volume":"66","author":"Spiess","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1517\/17460441.2014.925875","article-title":"Novel targeted therapies for the treatment of penile cancer","volume":"9","author":"Agarwal","year":"2014","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/ijc.2910500505","article-title":"Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: A retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction","volume":"50","author":"Wiener","year":"1992","journal-title":"Int. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7873","DOI":"10.1038\/sj.onc.1203244","article-title":"The retinoblastoma gene family in differentiation and development","volume":"18","author":"Lipinski","year":"1999","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaad.2012.12.973","article-title":"Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression","volume":"69","author":"Mannweiler","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Buonerba, C., Pagliuca, M., Vitrone, F., Ascione, I., Elefante, I., Riccio, V., Romano, F., de Placido, S., and di Lorenzo, G. (2017). Immunotherapy for penile cancer. Future Sci.","DOI":"10.4155\/fsoa-2017-0031"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2174\/1389557517666170228115324","article-title":"Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer Types","volume":"17","author":"Kruk","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00428-010-1007-4","article-title":"Alterations in the tumor suppressor gene p16INK4A are associated with aggressive behavior of penile carcinomas","volume":"458","author":"Poetsch","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/1078-0432.CCR-1032-3","article-title":"Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis","volume":"10","author":"Golijanin","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00281-013-0363-y","article-title":"Resolution of inflammation as a novel chemopreventive strategy","volume":"35","author":"Lee","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.1116221","article-title":"Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-\u03b2-catenin signaling axis","volume":"310","author":"Castellone","year":"2005","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2008.02259.x","article-title":"Detection of HPV-DNA, p53 alterations, and methylation in penile squamous cell carcinoma in Japanese men","volume":"58","author":"Yanagawa","year":"2008","journal-title":"Pathol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/modpathol.2017.26","article-title":"HPV-negative penile squamous cell carcinoma: Disruptive mutations in the TP53 gene are common","volume":"30","author":"Kashofer","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0002-9440(10)62506-0","article-title":"Detection and typing of human papillomavirus DNA in penile carcinoma: Evidence for multiple independent pathways of penile carcinogenesis","volume":"159","author":"Rubin","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1470-2045(07)70137-7","article-title":"Molecular and genetic pathways in penile cancer","volume":"8","author":"Kayes","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/path.1394","article-title":"Evidence for at least three alternative mechanisms targeting the p16INK4A\/cyclin D\/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus","volume":"201","author":"Ferreux","year":"2003","journal-title":"J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1016\/S0140-6736(15)00239-1","article-title":"Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2\/3: A randomised, double-blind, placebo-controlled phase 2b trial","volume":"386","author":"Trimble","year":"2015","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1200\/JCO.2014.58.9093","article-title":"Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus\u2013Targeted Tumor-Infiltrating T Cells","volume":"33","author":"Draper","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1093\/annonc\/mdw216","article-title":"Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: Potential opportunities for immunotherapeutic approaches","volume":"27","author":"Udager","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.juro.2016.09.088","article-title":"Expression of Programmed Death Ligand 1 in Penile Cancer is of Prognostic Value and Associated with HPV Status","volume":"197","author":"Ottenhof","year":"2017","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Stankiewicz, E., Prowse, D.M., Ng, M., Cuzick, J., Mesher, D., Hiscock, F., Lu, Y.J., Watkin, N., Corbishley, C., and Lam, W. (2011). Alternative HER\/PTEN\/Akt pathway activation in HPV positive and negative penile carcinomas. PLoS ONE.","DOI":"10.1371\/journal.pone.0017517"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1016\/j.humpath.2013.07.012","article-title":"The epidermal growth factor receptor is frequently overexpressed in penile squamous cell carcinomas: A tissue microarray and digital image analysis study of 112 cases","volume":"44","author":"Chaux","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1158\/0008-5472.CAN-15-1004","article-title":"Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy","volume":"75","author":"McDaniel","year":"2015","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e650","DOI":"10.1200\/JCO.2011.34.8367","article-title":"Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis","volume":"29","author":"Necchi","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/bju.12450","article-title":"Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis","volume":"113","author":"Carthon","year":"2014","journal-title":"BJU Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1517\/14712598.2015.993377","article-title":"The epidermal growth factor receptors as biological targets in penile cancer","volume":"15","author":"Buonerba","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Buonerba, C., di Lorenzo, G., Pond, G., Carteni, G., Scagliarini, S., Rozzi, A., Quevedo, F.J., Dorff, T., Nappi, L., and Lanzetta, G. (2016). Prognostic and Predictive Factors in Patients with Advanced Penile Cancer Receiving Salvage (2nd or Later Line) Systemic Treatment: A Retrospective, Multi-Center Study. Front. Pharmacol.","DOI":"10.3389\/fphar.2016.00487"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1159\/000315432","article-title":"Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: A preliminary report","volume":"85","author":"Zhu","year":"2010","journal-title":"Urol. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.juro.2007.12.040","article-title":"PIK3CA, HRAS and KRAS gene mutations in human penile cancer","volume":"179","author":"Andersson","year":"2008","journal-title":"J. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Necchi, A., Raggi, D., Giannatempo, P., Nicolai, N., Colecchia, M., Calareso, G., Togliardi, E., Crippa, F., Mariani, L., and Perrone, F. (2016). 239 Pan-HER trosine-kinase inhibitors (TKI) dacomitinib and afatinib in penile squamous cell carcinoma (PSCC): Results from an ongoing open-label, single-group, phase 2 trial of dacomitinib in chemonaive patients (pts). Eur. Urol. Suppl.","DOI":"10.1016\/S1569-9056(16)60241-5"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1244","DOI":"10.1016\/S1569-9056(17)30773-X","article-title":"Dacomitinib (Daco) induction therapy for locally-advanced (LA) or metastatic penile squamous cell carcinoma (PSCC): An open label, single-arm, phase 2 study","volume":"16","author":"Necchi","year":"2017","journal-title":"Eur. Urol. Suppl."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5985","DOI":"10.1038\/sj.onc.1209625","article-title":"MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors","volume":"25","author":"Peter","year":"2006","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e702","DOI":"10.1016\/S1569-9056(15)60694-7","article-title":"702 Epigenomics of penile squamous cell carcinoma","volume":"14","author":"Feber","year":"2015","journal-title":"Eur. Urol. Suppl."},{"key":"ref_59","unstructured":"Necchi, A., Eigl, B.J., Yang, E.S.-H., Bae, S., Chandrashekar, D., Chen, D., Naik, G., Mehta, A., Giannatempo, P., and Colecchia, M. (2016). Gene Expression Profiling of Advanced Penile Squamous Cell Carcinoma Receiving Cisplatin-based Chemotherapy Improves Prognostication and Identifies Potential Therapeutic Targets. Eur. Urol. Focus."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e240","DOI":"10.1016\/S1569-9056(16)60242-7","article-title":"240 Distinct patterns of copy number aberrations in penile cancer","volume":"15","author":"Rodney","year":"2016","journal-title":"Eur. Urol. Suppl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1158\/1940-6207.CAPR-14-0284","article-title":"Genomic profiling of human penile carcinoma predicts worse prognosis and survival","volume":"8","author":"Marchi","year":"2015","journal-title":"Cancer Prev. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wei, P., Shen, X., Zhang, Y., Xu, B., Zhou, J., Fan, S., Hao, Z., Shi, H., and Zhang, X. (2015). MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing. PLoS ONE.","DOI":"10.1371\/journal.pone.0131336"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.juro.2016.01.115","article-title":"Integrated Loss of miR-1\/miR-101\/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient Outcome","volume":"196","author":"Hartz","year":"2016","journal-title":"J. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10791","DOI":"10.3390\/ijms140610791","article-title":"Epigenetic mechanisms in penile carcinoma","volume":"14","author":"Kuasne","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1158\/1078-0432.CCR-14-1656","article-title":"Epigenetics markers of metastasis and HPV-induced tumorigenesis in penile cancer","volume":"21","author":"Feber","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1365-2133.2006.07604.x","article-title":"Inactivation of the CDKN2A and the p53 tumour suppressor genes in external genital carcinomas and their precursors","volume":"156","author":"Soufir","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1464-410X.2008.07603.x","article-title":"Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma","volume":"102","author":"Guerrero","year":"2008","journal-title":"BJU Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7065","DOI":"10.1158\/0008-5472.CAN-05-1783","article-title":"MicroRNA gene expression deregulation in human breast cancer","volume":"65","author":"Iorio","year":"2005","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15294","DOI":"10.18632\/oncotarget.14783","article-title":"Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact","volume":"8","author":"Kuasne","year":"2017","journal-title":"Oncotarget"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1777\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:42:30Z","timestamp":1760208150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,16]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081777"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081777","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,16]]}}}