1. 3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
- Author
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Kevin Fung, Mohammed Imran Khan, Temitope Akintola, Luc G. T. Morris, Anthony C. Nichols, Paul C. Boutros, Hugh Andrew Jinwook Kim, Joe S. Mymryk, Peter Y.F. Zeng, Xiaoxiao Deng, Halema Khan, Laura Jarycki, Mark Lee, Danielle MacNeil, David A. Palma, Krupal B. Patel, Pencilla Lang, Alana Sorgini, Adrian Mendez, John W. Barrett, Mushfiq Hassan Shaikh, and John Yoo
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Oncology and Carcinogenesis ,mutational status ,Article ,chromosome loss ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,microRNA ,Genetics ,medicine ,genomics ,2.1 Biological and endogenous factors ,HRAS ,Stage (cooking) ,RC254-282 ,Cancer ,030304 developmental biology ,0303 health sciences ,copy number alterations ,business.industry ,Human Genome ,Head and neck cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,3. Good health ,Infectious Diseases ,030220 oncology & carcinogenesis ,Chromosome Arm ,Cohort ,Sexually Transmitted Infections ,Biomarker (medicine) ,head and neck cancer ,business ,Biotechnology - Abstract
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 (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
- 2021