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A composite profile combining CD147 with infiltrating CD15+ cells in an HPV-driven context shows the strongest predictive 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tumor microenvironment biomarkers were evaluated for their association with penile cancer progression?","Question",{"text":62,"@type":63},"The study evaluates HPV, p63, CD15, DKK1, and CD147 and links them to a tumor-promoting TME and higher TNM classification in more aggressive disease.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How were the relationships between biomarkers and outcomes analyzed?",{"text":67,"@type":63},"Correlations and association analyses were performed using immune-reactive scores (IRS) from tissue microarray staining, followed by Kaplan–Meier survival estimates and Cox regression analyses to assess survival impact.",{"name":69,"@type":60,"acceptedAnswer":70},"What biomarker combination showed the strongest predictive power?",{"text":71,"@type":63},"The combination of CD147 with infiltrating CD15+ cells in an active HPV-driven transformation displayed the strongest prognosis signal, and the HPV + CD147 + CD15+ status was identified as the most potent 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nature.com/scientificreports)  \nOPEN  \nThe impact of the tumor microenvironment on the survival of penile cancer patients  \nStefan Lohse1,11*, Jan Niklas Mink2, Lea Eckhart3, Muriel Charlotte Hans1, Leuart Jusufi1, Anabel Zwick1, Tobias Mohr1, Isabelle Ariane Bley1, Oybek Khalmurzaev2,4,  \nVsevolod Borisovich Matveev4, Philine Loertzer5, Alexey Pryalukhin6, Arndt Hartmann7, Carol‑Immanuel Geppert7, Hagen Loertzer 5, Heiko Wunderlich8, Hans‑Peter Lenhof3, Carsten Maik Naumann9, Holger Kalthoff10 & Kerstin Junker2  \nPeCa is a rare entity with rising incidence rates due to increased infections with human papillomaviruses (HPV). The distinct subtypes of PeCa with an individual pathogenesis demand biomarkers for a precise patient risk assessment regarding disease progression and therapeutic susceptibility. We recently identified promising candidates associated with an HPV‑instructed tumor microenvironment (TME) using HPV‑positive PeCa cell lines and tissue microarrays (TMA) . The capacity of HPV + p63 + PeCa cells to release neutrophil‑attracting CXCL‑8 provided a molecular link explaining the infiltration of CD15 + myeloid cells in PeCa specimens. The candidate biomarkers HPV, p63, CD15, DKK1, and CD147 linked a tumor‑promoting TME with a higher TNM classification reflecting more aggressive and metastasizing cancers. Based on immune‑reactive scores (IRS) from TMA staining for these biomarkers, we calculated correlations and conducted association analyses to assess the degree of relationship between all biomarkers. We then conducted Kaplan–Meier survival estimates and Cox regression analyses to delineate the impact on PeCa patient survival. There is a notable predictive potential regarding the survival of patients with biomarker profiles beyond the potency of the individual biomarker. From all candidate biomarkers and biomarker profiles, the combination of CD147 and infiltrating CD15 + cells linked to an active HPV‑driven transformation displayed cancer‑immune dynamics with dismal prognosis for patients. After deciphering relevant interdependencies, the HPV + CD147 + CD15 + status was the most potent profile predicting metastasis‑free survival of PeCa patients. The results of this report underscore the need for analysis of the TME and the development of multi‑parameter composite scores that reflect fundamental cancer‑ immune relationships to tailor therapeutic interventions based on actual cancer immune dynamics.  \nKeywords Penile cancer, HPV, Neutrophils, Survival, CD147, Tumor microenvironment  \nThe reorganization of the TME towards a tumor-promoting environment composed of different supporting cellular species belongs to the hallmarks of cancer1,2. The TME comprises cellular and non-cellular elements surrounding and embedding tumor cells including the extracellular matrix, a specific cytokine configuration and different types of immune, stromal, and vascular cells. Heterogeneity, angiogenesis, immunosuppression, and a certain level of cellular plasticity regarding phenotypes and functional properties contribute to the TMEs  \n1Institute for Virology, Saarland University Medical Center, Saarland University, Kirrberger Str. Building 47, 66421 Homburg, Germany. 2Department of Urology and Pediatric Urology, Saarland University, 66421 Homburg, Germany. 3Center for Bioinformatics, Saarland Informatics Campus, Saarland University, Saarbrücken, Germany. 4Department of Urology, Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology”, Ministry of Health of the Russian Federation, Moscow 115478, Russian Federation. 5Department of Urology and Pediatric Urology, Westpfalz-Klinikum, Kaiserslautern, Germany. 6Institute of Pathology, Saarland University Medical Centre, 66421 Homburg, Germany. 7Institute of Pathology, University Erlangen-Nuremberg, 91054 Erlangen, Germany. 8Clinic of Urology and Pediatric Urology, St. Georg Klinikum, 99817 Eisenach, Germany. 9Depart","cbCaitdTeqlCQAvp","https://ap.wps.com/l/cbCaitdTeqlCQAvp","pdf",1663943,13,"English","# Introduction\n## Tumor microenvironment and cancer hallmarks\n## Penile cancer epidemiology and HPV links\n# Methods and biomarkers\n## Biomarker selection and immune-reactive scoring\n## Correlation and association analyses\n## Kaplan–Meier and Cox regression\n# Results and clinical implications\n## CD147/CD15+ HPV-driven predictive profiles\n## Composite scores for therapy tailoring","[{\"question\":\"Which tumor microenvironment biomarkers were evaluated for their association with penile cancer progression?\",\"answer\":\"The study evaluates HPV, p63, CD15, DKK1, and CD147 and links them to a tumor-promoting TME and higher TNM classification in more aggressive disease.\"},{\"question\":\"How were the relationships between biomarkers and outcomes analyzed?\",\"answer\":\"Correlations and association analyses were performed using immune-reactive scores (IRS) from tissue microarray staining, followed by Kaplan–Meier survival estimates and Cox regression analyses to assess survival impact.\"},{\"question\":\"What biomarker combination showed the strongest predictive power?\",\"answer\":\"The combination of CD147 with infiltrating CD15+ cells in an active HPV-driven transformation displayed the strongest prognosis signal, and the HPV + CD147 + CD15+ status was identified as the most potent profile predicting metastasis-free survival.\"}]","The impact of the tumor microenvironment on the survival of penile cancer patients | PDF",1790034576,33]