Mohd Faizal Nur Fatinazwa, Vincent-Chong Vui King, Ramanathan Anand, Paterson Ian C, Karen-Ng Lee Peng, Zaini Zuraiza Mohamad
Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Biomedicines. 2024 Dec 19;12(12):2899. doi: 10.3390/biomedicines12122899.
Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, and non-dysplastic lesions may also undergo malignant transformation. Oral carcinogenesis is a complex molecular process that involves somatic alterations and the deregulation of transcriptions, protein expression, and metabolite levels. Metabolomics, which is the scientific study of metabolites, has emerged as a promising high-throughput approach to investigate the metabolic changes of small molecules in biological pathways. In this review, we summarize the data relating to the metabolomic profiling of OPMDs, which will help elucidate the complex process of oral carcinogenesis. Furthermore, we identify that among all metabolites, citrate, pyruvate, and glutamate may serve as potential biomarkers for oral leukoplakia (OLK). Notably, metformin and gluconate have been shown to target glutamate and citrate, respectively, in cancer cells. Based on these findings, we propose that targeting these metabolites in patients with OPMD could be a promising therapeutic strategy to mitigate OPMD progression and potentially reduce the risk of malignant transformation. We also discuss the limitations and future directions of metabolomics in OPMD. Understanding these important metabolites is crucial for early detection and monitoring of oral cancer progression.
口腔潜在恶性疾病(OPMD)是一组有发展为癌症风险的病变。预测哪些病变更有可能发生恶性转化的金标准是组织学上存在发育异常。然而,并非所有发育异常的病变都会进展,非发育异常的病变也可能发生恶性转化。口腔癌发生是一个复杂的分子过程,涉及体细胞改变以及转录、蛋白质表达和代谢物水平的失调。代谢组学是对代谢物进行科学研究,已成为一种有前景的高通量方法,用于研究生物途径中小分子的代谢变化。在本综述中,我们总结了与OPMD代谢组学分析相关的数据,这将有助于阐明口腔癌发生的复杂过程。此外,我们确定在所有代谢物中,柠檬酸、丙酮酸和谷氨酸可能作为口腔白斑(OLK)的潜在生物标志物。值得注意的是,二甲双胍和葡萄糖酸盐已分别被证明在癌细胞中作用于谷氨酸和柠檬酸。基于这些发现,我们提出在OPMD患者中针对这些代谢物可能是一种有前景的治疗策略,以减轻OPMD进展并潜在降低恶性转化风险。我们还讨论了代谢组学在OPMD中的局限性和未来方向。了解这些重要的代谢物对于口腔癌进展的早期检测和监测至关重要。