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Article

Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma

by
Laura D. Locati
1,†,
Mara S. Serafini
2,†,
Maria F. Iannò
2,
Andrea Carenzo
2,
Ester Orlandi
3,
Carlo Resteghini
1,
Stefano Cavalieri
1,
Paolo Bossi
1,
Silvana Canevari
2,
Lisa Licitra
1,4 and
Loris De Cecco
2,*
1
Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
2
Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
3
Radiation Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
4
Department of Oncology, University of Milan, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
†
Authors contributed equally to this paper.
Cancers 2019, 11(8), 1057; https://doi.org/10.3390/cancers11081057
Submission received: 10 July 2019 / Revised: 21 July 2019 / Accepted: 24 July 2019 / Published: 26 July 2019
(This article belongs to the Special Issue Application of Bioinformatics in Cancers)
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Abstract

Patients (pts) with head and neck squamous cell carcinoma (HNSCC) have different epidemiologic, clinical, and outcome behaviors in relation to human papillomavirus (HPV) infection status, with HPV-positive patients having a 70% reduction in their risk of death. Little is known about the molecular heterogeneity in HPV-related cases. In the present study, we aim to disclose the molecular subtypes with potential biological and clinical relevance. Through a literature review, 11 studies were retrieved with a total of 346 gene-expression data points from HPV-positive HNSCC pts. Meta-analysis and self-organizing map (SOM) approaches were used to disclose relevant meta-gene portraits. Unsupervised consensus clustering provided evidence of three biological subtypes in HPV-positive HNSCC: Cl1, immune-related; Cl2, epithelial–mesenchymal transition-related; Cl3, proliferation-related. This stratification has a prognostic relevance, with Cl1 having the best outcome, Cl2 the worst, and Cl3 an intermediate survival rate. Compared to recent literature, which identified immune and keratinocyte subtypes in HPV-related HNSCC, we confirmed the former and we separated the latter into two clusters with different biological and prognostic characteristics. At present, this paper reports the largest meta-analysis of HPV-positive HNSCC studies and offers a promising molecular subtype classification. Upon further validation, this stratification could improve patient selection and pave the way for the development of a precision medicine therapeutic approach.
Keywords: self-organizing map; head and neck cancer; treatment de-escalation; HP; molecular subtypes; tumor microenvironment self-organizing map; head and neck cancer; treatment de-escalation; HP; molecular subtypes; tumor microenvironment

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MDPI and ACS Style

Locati, L.D.; Serafini, M.S.; Iannò, M.F.; Carenzo, A.; Orlandi, E.; Resteghini, C.; Cavalieri, S.; Bossi, P.; Canevari, S.; Licitra, L.; et al. Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma. Cancers 2019, 11, 1057. https://doi.org/10.3390/cancers11081057

AMA Style

Locati LD, Serafini MS, Iannò MF, Carenzo A, Orlandi E, Resteghini C, Cavalieri S, Bossi P, Canevari S, Licitra L, et al. Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma. Cancers. 2019; 11(8):1057. https://doi.org/10.3390/cancers11081057

Chicago/Turabian Style

Locati, Laura D., Mara S. Serafini, Maria F. Iannò, Andrea Carenzo, Ester Orlandi, Carlo Resteghini, Stefano Cavalieri, Paolo Bossi, Silvana Canevari, Lisa Licitra, and et al. 2019. "Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma" Cancers 11, no. 8: 1057. https://doi.org/10.3390/cancers11081057

APA Style

Locati, L. D., Serafini, M. S., Iannò, M. F., Carenzo, A., Orlandi, E., Resteghini, C., Cavalieri, S., Bossi, P., Canevari, S., Licitra, L., & De Cecco, L. (2019). Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma. Cancers, 11(8), 1057. https://doi.org/10.3390/cancers11081057

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