J Cancer 2021; 12(5):1563-1574. doi:10.7150/jca.54252

Research Paper

Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions

Xun Chen1#, Chen Yi1#, Man-Jun Yang2, Xueqi Sun3*, Xubin Liu3, Hanyu Ma3, Yiming Li1, Hongyu Li1, Chao Wang1, Yi He1, Guanhui Chen1, Shangwu Chen4, Li Yu3, Dongsheng Yu1✉

1. Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, People's Republic of China.
2. Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
3. Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
4. Guangdong Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
#These authors contributed equally to this work.
*Present address: Ganzhou People's Hospital.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Chen X, Yi C, Yang MJ, Sun X, Liu X, Ma H, Li Y, Li H, Wang C, He Y, Chen G, Chen S, Yu L, Yu D. Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions. J Cancer 2021; 12(5):1563-1574. doi:10.7150/jca.54252. Available from https://www.jcancer.org/v12p1563.htm

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Background: Most tumors have an enhanced glycolysis flux, even when oxygen is available, called the aerobic glycolysis or the Warburg effect. Metabolic reprogramming promotes cancer progression, and is even related to the tumorigenesis. However, it is not clear whether the observed metabolic changes act as a driver or a bystander in cancer development.

Methods: In this study, the metabolic characteristics of oral precancerous cells and cervical precancerous lesions were analyzed by metabolomics, and the expression of glycolytic enzymes in cervical precancerous lesions was evaluated by RT-PCR and Western blot analysis.

Results: In total, 115 and 23 metabolites with reliable signals were identified in oral cells and cervical tissues, respectively. Based on the metabolome, oral precancerous cell DOK could be clearly separated from normal human oral epithelial cells (HOEC) and oral cancer cells. Four critical differential metabolites (pyruvate, glutamine, methionine and lysine) were identified between DOK and HOEC. Metabolic profiles could clearly distinguish cervical precancerous lesions from normal cervical epithelium and cervical cancer. Compared with normal cervical epithelium, the glucose consumption and lactate production increased in cervical precancerous lesions. The expression of glycolytic enzymes LDHA, HK II and PKM2 showed an increased tendency in cervical precancerous lesions compared with normal cervical epithelium.

Conclusions: Our findings suggest that cell metabolism may be reprogrammed at the early stage of tumorigenesis, implying the contribution of metabolic reprogramming to the development of tumor.

Keywords: metabolic reprogramming, precancerous lesions, metabolomics, the Warburg-like effect, glycolytic enzymes