Author:
Zhou Zekun,Tang Jianfei,Lu Yixuan,Jia Jia,Luo Tiao,Su Kaixin,Dai Xiaohan,Zhang Haixia,Liu Ousheng
Abstract
Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC.
Methods
We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed.
Results
Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype.
Conclusion
The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.
Funder
the Fundamental Research Funds for the Central Universities of Central South University
Natural Science Foundation of Hunan Province
Key Research and Development Program of Hunan Province of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference62 articles.
1. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1):92.
2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209.
3. World Health Organization. Global Cancer Observatory: Cancer Tomorrow. 2020. Available online at:
https://gco.iarc.fr/tomorrow/en/dataviz/isotype. Accessed 25 Mar 2021.
4. Erkal H, Mendenhall W, Amdur R, Villaret D, Stringer S. Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol Off Journal Am Soc Clin Oncol. 2001;19(5):1358–62.
5. Domingo-Vidal M, Whitaker-Menezes D, Martos-Rus C, Tassone P, Snyder CM, Tuluc M, Philp N, Curry J, Martinez-Outschoorn U. Cigarette smoke induces metabolic reprogramming of the tumor stroma in head and neck squamous cell carcinoma. Mol Cancer Res. 2019;17(9):1893–909.
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