3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

Hugh Andrew Jinwook Kim; Mushfiq Hassan Shaikh; Mark Lee; Peter Y. F. Zeng; Alana Sorgini; Temitope Akintola; Xiaoxiao Deng; Laura Jarycki; Halema Khan; Danielle MacNeil; Mohammed Imran Khan; Adrian Mendez; John Yoo; Kevin Fung; Pencilla Lang; David A. Palma; Krupal Patel; Joe S. Mymryk; John W. Barrett; Paul C. Boutros; Luc G. T. Morris; Anthony C. Nichols

doi:10.3390/cancers13215313

Cancers (Oct 2021)

3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

Hugh Andrew Jinwook Kim,
Mushfiq Hassan Shaikh,
Mark Lee,
Peter Y. F. Zeng,
Alana Sorgini,
Temitope Akintola,
Xiaoxiao Deng,
Laura Jarycki,
Halema Khan,
Danielle MacNeil,
Mohammed Imran Khan,
Adrian Mendez,
John Yoo,
Kevin Fung,
Pencilla Lang,
David A. Palma,
Krupal Patel,
Joe S. Mymryk,
John W. Barrett,
Paul C. Boutros,
Luc G. T. Morris,
Anthony C. Nichols

Affiliations

Hugh Andrew Jinwook Kim: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Mushfiq Hassan Shaikh: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Mark Lee: Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY 10065, USA
Peter Y. F. Zeng: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Alana Sorgini: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Temitope Akintola: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Xiaoxiao Deng: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Laura Jarycki: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Halema Khan: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Danielle MacNeil: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Mohammed Imran Khan: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Adrian Mendez: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
John Yoo: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Kevin Fung: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Pencilla Lang: Department of Oncology, University of Western Ontario, London, ON N6A3K7, Canada
David A. Palma: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Krupal Patel: Moffitt Cancer Center, Department of Otolaryngology, Tampa, FL 33612, USA
Joe S. Mymryk: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
John W. Barrett: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada
Paul C. Boutros: Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
Luc G. T. Morris: Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY 10065, USA
Anthony C. Nichols: Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON N6A3K7, Canada

DOI: https://doi.org/10.3390/cancers13215313
Journal volume & issue: Vol. 13, no. 21
p. 5313

Abstract

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Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had 97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid–non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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