Jose P Zevallos1, Angela L Mazul1, Vonn Walter2, David Neil Hayes3. 1. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri. 2. Penn State Hershey Institute for Personalized Medicine, Hershey, Pennsylvania. 3. Department of Medical Oncology, University of Tennessee Health Sciences West Cancer Center, Memphis, Tennessee, U.S.A.
Abstract
OBJECTIVES/HYPOTHESIS: Gene expression analyses of head and neck cancer have revealed four molecular subtypes: basal (BA), mesenchymal (MS), atypical (AT), and classical (CL). We evaluate whether gene expression subtypes in oral cavity squamous cell carcinoma (OCSCC) and laryngeal squamous cell carcinoma (LSCC) can be used to predict nodal metastasis and prognosticate survival. STUDY DESIGN: Retrospective cohort study and genomic analysis. METHODS: OCSCC and LSCC cases were identified from the The Cancer Genome Atlas (TCGA) head and neck cancer cohort. RNA-seq by expected maximization (RSEM) was used to quantify gene expression levels from TCGA RNA-seq data and to assign each case to one of four subtypes. Descriptive statistics were used to describe patient, disease, and treatment characteristics in each subtype. Cox regression and Kaplan-Meier analyses were used to determine associations with survival. RESULTS: OCSCC cases were comprised primarily of the MS and BA subtypes, whereas LSCC was comprised primarily of CL and AT subtypes. In OCSCC, the MS subtype was significantly associated with higher risk of nodal metastasis. In a subset analysis of clinically T1-2N0M0 OCSCC, we demonstrate that the MS subtype was predictive of occult nodal metastasis (relative risk = 3.38, 95% confidence interval [CI]: 1.08-10.69). In LSCC, the CL subtype was associated with significantly worse overall survival (hazard ratio = 4.32, 95% CI: 1.77-10.54, P = .001). CONCLUSIONS: Gene expression analysis reveals potential novel markers of nodal metastasis and survival in human papillomavirus-negative head and neck cancer. Future studies will continue to refine and validate these markers, with the goal of providing molecular risk assessments that guide therapy and improve patient outcomes. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:154-161, 2019.
OBJECTIVES/HYPOTHESIS: Gene expression analyses of head and neck cancer have revealed four molecular subtypes: basal (BA), mesenchymal (MS), atypical (AT), and classical (CL). We evaluate whether gene expression subtypes in oral cavity squamous cell carcinoma (OCSCC) and laryngeal squamous cell carcinoma (LSCC) can be used to predict nodal metastasis and prognosticate survival. STUDY DESIGN: Retrospective cohort study and genomic analysis. METHODS:OCSCC and LSCC cases were identified from the The Cancer Genome Atlas (TCGA) head and neck cancer cohort. RNA-seq by expected maximization (RSEM) was used to quantify gene expression levels from TCGA RNA-seq data and to assign each case to one of four subtypes. Descriptive statistics were used to describe patient, disease, and treatment characteristics in each subtype. Cox regression and Kaplan-Meier analyses were used to determine associations with survival. RESULTS:OCSCC cases were comprised primarily of the MS and BA subtypes, whereas LSCC was comprised primarily of CL and AT subtypes. In OCSCC, the MS subtype was significantly associated with higher risk of nodal metastasis. In a subset analysis of clinically T1-2N0M0 OCSCC, we demonstrate that the MS subtype was predictive of occult nodal metastasis (relative risk = 3.38, 95% confidence interval [CI]: 1.08-10.69). In LSCC, the CL subtype was associated with significantly worse overall survival (hazard ratio = 4.32, 95% CI: 1.77-10.54, P = .001). CONCLUSIONS: Gene expression analysis reveals potential novel markers of nodal metastasis and survival in human papillomavirus-negative head and neck cancer. Future studies will continue to refine and validate these markers, with the goal of providing molecular risk assessments that guide therapy and improve patient outcomes. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:154-161, 2019.
Authors: K Kian Ang; Jonathan Harris; Richard Wheeler; Randal Weber; David I Rosenthal; Phuc Felix Nguyen-Tân; William H Westra; Christine H Chung; Richard C Jordan; Charles Lu; Harold Kim; Rita Axelrod; C Craig Silverman; Kevin P Redmond; Maura L Gillison Journal: N Engl J Med Date: 2010-06-07 Impact factor: 91.245
Authors: Matthew D Wilkerson; Xiaoying Yin; Katherine A Hoadley; Yufeng Liu; Michele C Hayward; Christopher R Cabanski; Kenneth Muldrew; C Ryan Miller; Scott H Randell; Mark A Socinski; Alden M Parsons; William K Funkhouser; Carrie B Lee; Patrick J Roberts; Leigh Thorne; Philip S Bernard; Charles M Perou; D Neil Hayes Journal: Clin Cancer Res Date: 2010-07-19 Impact factor: 12.531
Authors: Kristina R Dahlstrom; Gabriel Calzada; Jennifer D Hanby; Adam S Garden; Bonnie S Glisson; Guojun Li; Dianna B Roberts; Randal S Weber; Erich M Sturgis Journal: Cancer Date: 2012-06-26 Impact factor: 6.860
Authors: Sabrina Daniela da Silva; Grégoire B Morand; Faisal A Alobaid; Michael P Hier; Alex M Mlynarek; Moulay A Alaoui-Jamali; Luiz Paulo Kowalski Journal: Clin Exp Metastasis Date: 2014-11-30 Impact factor: 5.150
Authors: Curtis R Pickering; Jiexin Zhang; Suk Young Yoo; Linnea Bengtsson; Shhyam Moorthy; David M Neskey; Mei Zhao; Marcus V Ortega Alves; Kyle Chang; Jennifer Drummond; Elsa Cortez; Tong-Xin Xie; Di Zhang; Woonbok Chung; Jean-Pierre J Issa; Patrick A Zweidler-McKay; Xifeng Wu; Adel K El-Naggar; John N Weinstein; Jing Wang; Donna M Muzny; Richard A Gibbs; David A Wheeler; Jeffrey N Myers; Mitchell J Frederick Journal: Cancer Discov Date: 2013-04-25 Impact factor: 39.397
Authors: Vonn Walter; Xiaoying Yin; Matthew D Wilkerson; Christopher R Cabanski; Ni Zhao; Ying Du; Mei Kim Ang; Michele C Hayward; Ashley H Salazar; Katherine A Hoadley; Karen Fritchie; Charles J Sailey; Charles G Sailey; Mark C Weissler; William W Shockley; Adam M Zanation; Trevor Hackman; Leigh B Thorne; William D Funkhouser; Kenneth L Muldrew; Andrew F Olshan; Scott H Randell; Fred A Wright; Carol G Shores; D Neil Hayes Journal: PLoS One Date: 2013-02-22 Impact factor: 3.240
Authors: Owen Willis; Khalil Choucair; Abdurahman Alloghbi; Laura Stanbery; Rex Mowat; F Charles Brunicardi; Lance Dworkin; John Nemunaitis Journal: Cancer Gene Ther Date: 2020-01-28 Impact factor: 5.987