Evaluation of metabolite biomarkers for hepatocellular carcinoma through stratified analysis by gender, race, and alcoholic cirrhosis

Junfeng Xiao, Yi Zhao, Rency S. Varghese, Bin Zhou, Cristina Di Poto, Lihua Zhang, Mahlet G. Tadesse, Dina Hazem Ziada, Kirti Shetty, Habtom W. Ressom

Research output: Contribution to journalArticle

Abstract

Background: The effects of hepatocellular carcinoma on liver metabolism and circulating metabolites have been subjected to continuing investigation. This study compares the levels of selected metabolites in sera of hepatocellular carcinoma cases versus patients with liver cirrhosis and evaluates the influence of gender, race, and alcoholic cirrhosis on the performance of the metabolites as candidate biomarkers for hepatocellular carcinoma. Methods: Targeted quantitation of 15 metabolites is performed by selected research monitoring in sera from 89 Egyptian subjects (40 hepatocellular carcinoma cases and 49 cirrhotic controls) and 110 U.S. subjects (56 hepatocellular carcinoma cases and 54 cirrhotic controls). Logistic regression models are used to evaluate the ability of these metabolites in distinguishing hepatocellular carcinoma cases from cirrhotic controls. The influences of gender, race, and alcoholic cirrhosis on the performance of the metabolites are analyzed by stratified logistic regression. Results: Two metabolites are selected on the basis of their significance to both cohorts. Although both metabolites discriminate hepatocellular carcinoma cases from cirrhotic controls in males and Caucasians, they are insignificant in females and African Americans. One metabolite is significant in patients with alcoholic cirrhosis and the other in nonalcoholic cirrhosis. Conclusions: The study demonstrates the potential of two metabolites as candidate biomarkers for hepatocellular carcinoma by combining them with a-fetoprotein (AFP) and gender. Stratified statistical analyses reveal that gender, race, and alcoholic cirrhosis affect the relative levels of small molecules in serum. Impact: The findings of this study contribute to a better understanding of the influence of gender, race, and alcoholic cirrhosis in investigating small molecules as biomarkers for hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev; 23(1); 64-72.

Original languageEnglish (US)
Pages (from-to)64-72
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2014

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Xiao, J., Zhao, Y., Varghese, R. S., Zhou, B., Di Poto, C., Zhang, L., Tadesse, M. G., Ziada, D. H., Shetty, K., & Ressom, H. W. (2014). Evaluation of metabolite biomarkers for hepatocellular carcinoma through stratified analysis by gender, race, and alcoholic cirrhosis. Cancer Epidemiology Biomarkers and Prevention, 23(1), 64-72. https://doi.org/10.1158/1055-9965.EPI-13-0327