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

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 even...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	head and neck cancer chromosome loss copy number alterations genomics mutational status Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d4456068f0a84cf58a6156b5ae7776c8
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spelling	oai:doaj.org-article:d4456068f0a84cf58a6156b5ae7776c82021-11-11T15:28:08Z3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset10.3390/cancers132153132072-6694https://doaj.org/article/d4456068f0a84cf58a6156b5ae7776c82021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5313https://doaj.org/toc/2072-6694Loss 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 <1% or >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 (<i>p</i> > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (<i>p</i> < 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.Hugh Andrew Jinwook KimMushfiq Hassan ShaikhMark LeePeter Y. F. ZengAlana SorginiTemitope AkintolaXiaoxiao DengLaura JaryckiHalema KhanDanielle MacNeilMohammed Imran KhanAdrian MendezJohn YooKevin FungPencilla LangDavid A. PalmaKrupal PatelJoe S. MymrykJohn W. BarrettPaul C. BoutrosLuc G. T. MorrisAnthony C. NicholsMDPI AGarticlehead and neck cancerchromosome losscopy number alterationsgenomicsmutational statusNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5313, p 5313 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	head and neck cancer chromosome loss copy number alterations genomics mutational status Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	head and neck cancer chromosome loss copy number alterations genomics mutational status Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
description	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 <1% or >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 (<i>p</i> > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (<i>p</i> < 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.
format	article
author	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
author_facet	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
author_sort	Hugh Andrew Jinwook Kim
title	3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
title_short	3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
title_full	3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
title_fullStr	3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
title_full_unstemmed	3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
title_sort	3p arm loss and survival in head and neck cancer: an analysis of tcga dataset
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d4456068f0a84cf58a6156b5ae7776c8
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3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

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