A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

Background. Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expr...

Full description

Saved in:
Bibliographic Details
Main Authors: Zeng-Hong Wu, Yun Tang, Yue Zhou
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/6716908
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832551647587336192
author Zeng-Hong Wu
Yun Tang
Yue Zhou
author_facet Zeng-Hong Wu
Yun Tang
Yue Zhou
author_sort Zeng-Hong Wu
collection DOAJ
description Background. Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. Method. In this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy. Results. We extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR=1.144, 95% CI=1.044~1.251) and the lowest risk (HR=0.580, 95% CI=0.400~0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset. Conclusion. Taken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.
format Article
id doaj-art-08b3226a1c2d4e198efa76a8ed2d3a5d
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-08b3226a1c2d4e198efa76a8ed2d3a5d2025-02-03T06:00:48ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/67169086716908A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell CarcinomaZeng-Hong Wu0Yun Tang1Yue Zhou2Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaBackground. Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. Method. In this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy. Results. We extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR=1.144, 95% CI=1.044~1.251) and the lowest risk (HR=0.580, 95% CI=0.400~0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset. Conclusion. Taken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.http://dx.doi.org/10.1155/2020/6716908
spellingShingle Zeng-Hong Wu
Yun Tang
Yue Zhou
A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
Mediators of Inflammation
title A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
title_full A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
title_fullStr A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
title_short A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma
title_sort metabolic gene signature to predict overall survival in head and neck squamous cell carcinoma
url http://dx.doi.org/10.1155/2020/6716908
work_keys_str_mv AT zenghongwu ametabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma
AT yuntang ametabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma
AT yuezhou ametabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma
AT zenghongwu metabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma
AT yuntang metabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma
AT yuezhou metabolicgenesignaturetopredictoverallsurvivalinheadandnecksquamouscellcarcinoma