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

Chia Wei Hsu, Yi Ting Chen, Ya Ju Hsieh, Kai Ping Chang, Pei Chun Hsueh, Ting Wen Chen, Jau Song Yu, Yu Sun Chang, Liang Li, Chih Ching Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

35 Scopus citations

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.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalAnalytica Chimica Acta
Volume1050
DOIs
StatePublished - 07 03 2019

Bibliographical note

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

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

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