Serum metabolite profiling of a 4-Nitroquinoline-1-oxide-induced experimental oral carcinogenesis model using gas chromatography-mass spectrometry

BACKGROUND: Oral cancer progresses from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. The critical needs in oral cancer treatment are expanding our knowledge of malignant tumour progression and the development of useful approaches to prevent dysplastic lesions. This study was designed to gain insights into the underlying metabolic transformations that occur during the process of oral carcinogenesis. METHODS: We used gas chromatography-mass spectrometry (GC-MS) in conjunction with multivariate statistical techniques to observe alterations in serum metabolites in a 4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis model. Thirty-eight male rats were randomly divided into two groups, including the 4NQO-induced model group of 30 rats and the healthy control group of five rats. Animals were sacrificed at weeks 9, 13, 20, 24, and 32, post-4NQO treatment. Tissue samples were collected for histopathological examinations and blood samples were collected for metabolomic analysis. Partial least squares discriminate analysis (PLS-DA) models generated from GC-MS metabolic profile data showed robust discrimination from rats with oral premalignant and malignant lesions induced by 4NQO, and normal controls. RESULTS: The results found 16 metabolites associated with 4NQO-induced rat tongue carcinogenesis. Dysregulated arachidonic acid, fatty acid, and glycine metabolism, as well as disturbed tricarboxylic acid (TCA) cycle and mitochondrial respiratory chains were observed in the animal model. The PLS-DA models of metabolomic results demonstrated good separations between the 4NQO-induced model group and the normal control group. CONCLUSION: We found several metabolites modulated by 4NQO and provide a good reference for further study of early diagnosis in oral cancer.