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Hess, Julia; Unger, Kristian; Maihoefer, Cornelius; Schüttrumpf, Lars; Weber, Peter; Marschner, Sebastian; Wintergerst, Ludmila; Pflugradt, Ulrike; Baumeister, Philipp; Walch, Axel; Woischke, Christine; Kirchner, Thomas; Werner, Martin; Sörensen, Kristin; Baumann, Michael; Tinhofer, Ingeborg; Combs, Stephanie E.; Debus, Jürgen; Schäfer, Henning; Krause, Mechthild; Linge, Annett; von der Grün, Jens; Stuschke, Martin; Zips, Daniel; [...]

Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients

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  • Medientyp: E-Artikel
  • Titel: Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients
  • Beteiligte: Hess, Julia; Unger, Kristian; Maihoefer, Cornelius; Schüttrumpf, Lars; Weber, Peter; Marschner, Sebastian; Wintergerst, Ludmila; Pflugradt, Ulrike; Baumeister, Philipp; Walch, Axel; Woischke, Christine; Kirchner, Thomas; Werner, Martin; Sörensen, Kristin; Baumann, Michael; Tinhofer, Ingeborg; Combs, Stephanie E.; Debus, Jürgen; Schäfer, Henning; Krause, Mechthild; Linge, Annett; von der Grün, Jens; Stuschke, Martin; Zips, Daniel; [...]
  • Erschienen: MDPI AG, 2022
  • Erschienen in: Cancers
  • Sprache: Englisch
  • DOI: 10.3390/cancers14153745
  • ISSN: 2072-6694
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Human papillomavirus (HPV)-driven head and neck squamous cell carcinomas (HNSCC) generally have a more favourable prognosis. We hypothesized that HPV-associated HNSCC may be identified by an miRNA-signature according to their specific molecular pathogenesis, and be characterized by a unique transcriptome compared to HPV-negative HNSCC. We performed miRNA expression profiling of two p16/HPV DNA characterized HNSCC cohorts of patients treated by adjuvant radio(chemo)therapy (multicentre DKTK-ROG n = 128, single-centre LMU-KKG n = 101). A linear model predicting HPV status built in DKTK-ROG using lasso-regression was tested in LMU-KKG. LMU-KKG tumours (n = 30) were transcriptome profiled for differential gene expression and miRNA-integration. A 24-miRNA signature predicted HPV-status with 94.53% accuracy (AUC: 0.99) in DKTK-ROG, and 86.14% (AUC: 0.86) in LMU-KKG. The prognostic values of 24-miRNA- and p16/HPV DNA status were comparable. Combining p16/HPV DNA and 24-miRNA status allowed patient sub-stratification and identification of an HPV-associated patient subgroup with impaired overall survival. HPV-positive tumours showed downregulated MAPK, Estrogen, EGFR, TGFbeta, WNT signaling activity. miRNA-mRNA integration revealed HPV-specific signaling pathway regulation, including PD−L1 expression/PD−1 checkpoint pathway in cancer in HPV-associated HNSCC. Integration of clinically established p16/HPV DNA with 24-miRNA signature status improved clinically relevant risk stratification, which might be considered for future clinical decision-making with respect to treatment de-escalation in HPV-associated HNSCC.</jats:p>
  • Zugangsstatus: Freier Zugang