Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data

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 Expressio...

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Main Authors: Zekun Zhou, Jianfei Tang, Yixuan Lu, Jia Jia, Tiao Luo, Kaixin Su, Xiaohan Dai, Haixia Zhang, Ousheng Liu
Format: Article
Language:English
Published: BMC 2023-02-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-023-02880-3
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author Zekun Zhou
Jianfei Tang
Yixuan Lu
Jia Jia
Tiao Luo
Kaixin Su
Xiaohan Dai
Haixia Zhang
Ousheng Liu
author_facet Zekun Zhou
Jianfei Tang
Yixuan Lu
Jia Jia
Tiao Luo
Kaixin Su
Xiaohan Dai
Haixia Zhang
Ousheng Liu
author_sort Zekun Zhou
collection DOAJ
description 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.
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spelling doaj.art-6d825ce6051246f78fa98f39bf255c162023-03-22T12:26:30ZengBMCCancer Cell International1475-28672023-02-0123111610.1186/s12935-023-02880-3Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene dataZekun Zhou0Jianfei Tang1Yixuan Lu2Jia Jia3Tiao Luo4Kaixin Su5Xiaohan Dai6Haixia Zhang7Ousheng Liu8Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityThe Oncology Department of Xiangya Second Hospital, Central South UniversityHunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South UniversityAbstract 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.https://doi.org/10.1186/s12935-023-02880-3Bioinformatics1Metabolic classification2Prognosis3Head and neck squamous cell carcinoma4Glycolysis5Cholesterogenic6
spellingShingle Zekun Zhou
Jianfei Tang
Yixuan Lu
Jia Jia
Tiao Luo
Kaixin Su
Xiaohan Dai
Haixia Zhang
Ousheng Liu
Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
Cancer Cell International
Bioinformatics1
Metabolic classification2
Prognosis3
Head and neck squamous cell carcinoma4
Glycolysis5
Cholesterogenic6
title Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
title_full Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
title_fullStr Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
title_full_unstemmed Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
title_short Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
title_sort prognosis related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic cholesterogenic gene data
topic Bioinformatics1
Metabolic classification2
Prognosis3
Head and neck squamous cell carcinoma4
Glycolysis5
Cholesterogenic6
url https://doi.org/10.1186/s12935-023-02880-3
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