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Anal Chim Acta. 2019 Mar 7;1050:113-122. doi: 10.1016/j.aca.2018.10.070. Epub 2018 Nov 2.

Integrated analyses utilizing metabolomics and transcriptomics reveal perturbation of the polyamine pathway in oral cavity squamous cell carcinoma.

Author information

1
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
2
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
3
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
4
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
5
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
6
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
7
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: liang.li@ualberta.ca.
8
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: luckywu@mail.cgu.edu.tw.

Abstract

Oral cavity squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, is associated with poor prognosis and high mortality worldwide. Moreover, knowledge of the metabolic alterations that occur in OSCC is still limited. In the present study, we used a quantitative metabolomic approach with chemical isotope labeling (CIL) to analyze alterations in the metabolite levels in paired cancerous (T) and adjacent noncancerous (AN) tissues from 31 OSCC patients. Using volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we uncovered 99 dysregulated metabolites in OSCC and verified the identities of seven metabolites via comparison with authenticated standards. From these seven metabolites, we constructed a 3-marker panel, consisting of putrescine, glycyl-leucine, and phenylalanine, using a support vector machine (SVM) model that can discriminate T from AN with high sensitivity and specificity based on receiver operator characteristic (ROC) analysis. Furthermore, by integrating the metabolomics profiles with transcriptomics data obtained from the same sample set, we revealed the dysregulation of the polyamine pathway in OSCC. Our findings provide insights into the metabolic perturbations present in OSCC and have uncovered potential metabolic biomarkers and therapeutic targets for use in the treatment of OSCC.

KEYWORDS:

Cancer biomarker; Cancer tissue; Chemical isotope labeling; Metabolomics; Oral cavity squamous cell carcinoma; Polyamine pathway

PMID:
30661578
DOI:
10.1016/j.aca.2018.10.070
[Indexed for MEDLINE]

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