PMID- 30247749
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20200309
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 129
IP  - 1
DP  - 2019 Jan
TI  - Gene Expression Subtype Predicts Nodal Metastasis and Survival in Human 
      Papillomavirus-Negative Head and Neck Cancer.
PG  - 154-161
LID - 10.1002/lary.27340 [doi]
AB  - 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.
CI  - (c) 2018 The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Zevallos, Jose P
AU  - Zevallos JP
AUID- ORCID: 0000-0002-9111-6767
AD  - Department of Otolaryngology-Head and Neck Surgery, Washington University School 
      of Medicine in St. Louis, St. Louis, Missouri.
FAU - Mazul, Angela L
AU  - Mazul AL
AD  - Department of Otolaryngology-Head and Neck Surgery, Washington University School 
      of Medicine in St. Louis, St. Louis, Missouri.
FAU - Walter, Vonn
AU  - Walter V
AD  - Penn State Hershey Institute for Personalized Medicine, Hershey, Pennsylvania.
FAU - Hayes, David Neil
AU  - Hayes DN
AD  - Department of Medical Oncology, University of Tennessee Health Sciences West 
      Cancer Center, Memphis, Tennessee, U.S.A.
LA  - eng
GR  - R01 CA211939/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180924
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Neoplasm)
SB  - IM
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Carcinoma, Squamous Cell/*genetics/mortality
MH  - *Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Laryngeal Neoplasms/*genetics/mortality
MH  - Lymphatic Metastasis/genetics
MH  - Mouth Neoplasms/*genetics/mortality
MH  - Proportional Hazards Models
MH  - RNA, Neoplasm/analysis
MH  - Retrospective Studies
MH  - Sequence Analysis, RNA
PMC - PMC6320297
MID - NIHMS970071
OTO - NOTNLM
OT  - Oral cavity
OT  - RNA sequencing and gene expression subtype analysis
OT  - larynx
OT  - molecular biology
OT  - nodal metastasis
COIS- Conflicts of Interest: JPZ and DNH hold a provisional patent application based on 
      the findings presented in this manuscript
EDAT- 2018/09/25 06:00
MHDA- 2019/05/18 06:00
PMCR- 2020/01/01
CRDT- 2018/09/25 06:00
PHST- 2018/05/11 00:00 [accepted]
PHST- 2018/09/25 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2018/09/25 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.1002/lary.27340 [doi]
PST - ppublish
SO  - Laryngoscope. 2019 Jan;129(1):154-161. doi: 10.1002/lary.27340. Epub 2018 Sep 24.