Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis.

BACKGROUND: Oral Submucous fibrosis (OSF) is a chronic inflammatory mucosal disease of unknown etiology. Statistics show cases of OSF which has a high rate of overall prevalence and increase the chance of malignant transformation. As we know malignant cells is situated in a very complex microenvironment with altered metabolic pathway including intermediates which participate in oxidative stress process which enhances metabolic rewiring and promotes tumor progression. This study aims to evaluate the tumor microenvironment and their role in metabolic reprogramming. METHODS: This study was conducted on the serum sample of OSF (n = 20) compared to the healthy group (n = 20) using ELISA. The serum levels of intermediate by-products of metabolic pathway and oxidative stress induced biomolecular damage products were determined. The sensitivity of results was analyzed by correlating it with markers of metabolic status (Glucose, Total cholesterol, Total protein). RESULTS: Metabolic pathway intermediates molecules like Fatty Acids (FAA), Ascorbic acid, Citrate, Oxaloacetate (OAA), levels were significantly high in the serum of OSF cases. This indicated that intermediates act as a metabolic switch that drives cells to adapt malignant transformation pathway. Markers related to oxidative DNA damage (8-hydroxy-2' -deoxyguanosine), Oxidative lipid peroxidation (8-epi-Prostaglandin F2α), and Protein carbonyl were significantly up-regulated. This significant increase in oxidative stress marker revealed the reprogramming of the metabolic pathway for fulfilling the nutritional requirement of cancer cells. A further significant correlation was observed with metabolic products confirmed altered metabolic status. CONCLUSION: Our findings could identify the differentiating intermediate pathway metabolites and oxidative damage to biomolecules that are leading to rewiring of metabolism in the OSF group. Findings described in the study can be helpful to explain further the molecular aspects that lead to the progression of OSF towards carcinogenesis.

Delineating metabolic dysfunction in cellular metabolism of oral submucous fibrosis using 1H nuclear magnetic resonance spectroscopy.

OBJECTIVE: To delineate the metabolism involved in oral submucous fibrosis progression towards carcinogenesis by 1H nuclear magnetic resonance spectroscopy. METHODS: The proposed study was designed using 1H-NMR by comparing the metabolites in the serum sample of oral submucous fibrosis (n = 20) compared to the normal group (n = 20) using 1H nuclear magnetic resonance spectroscopy. Various statistical analysis like multivariate statistical analysis, Principle component analysis, Partial least squares Discriminant Analysis, Hierarchical cluster analysis was applied to analyze potential serum metabolites. RESULTS: The results generated from the principle component analysis, partial least squares discriminant analysis and hierarchical cluster analysis are sufficient to distinguish between oral submucous fibrosis group and normal group. A total of 15 significant metabolites associated with main pathways were identified, which correlated with the progression of cancer. Up-regulation of glucose metabolism-related metabolites indicated the high energy demand due to enhanced cell division rate in the oral submucous fibrosis group. A significant increase in lipid metabolism-related metabolites revealed the reprogramming of the fatty acids metabolic pathway to fulfilling the need for cell membrane formation in cancer cells. On the other hand, metabolites related to choline phosphocholine, the metabolic pathway was also altered. CONCLUSION: Our findings could identify the differentiating metabolites in the oral submucous fibrosis group. Significant alteration in metabolites in the oral submucous fibrosis group exhibited deregulation in metabolic events. The findings reported in the study can be beneficial to further explain the molecular aspects that lead to the progression of oral submucous fibrosis towards carcinogenesis.

Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry.

Oral submucous fibrosis (OSF) is found to have the highest malignant potentiality among all other pre-cancerous lesions. However, its detection prior to tissue biopsy can be challenging in clinics. Moreover, biopsy examination is invasive and painful. Hence, there is an urgent need of new technology that facilitates accurate diagnostic prediction of OSF prior to biopsy. Here, we used FTIR spectroscopy coupled with chemometric techniques to distinguish the serum metabolic signatures of OSF patients (n=30) and healthy controls (n=30). Serum biochemical analyses have been performed to further support the FTIR findings. Absorbance intensities of 45 infrared wavenumbers differed significantly between OSF and normal serum FTIR spectra representing alterations in carbohydrates, proteins, lipids and nucleic acids. Nineteen prominent significant wavenumbers (P≤0.001) at 1020, 1025, 1035, 1039, 1045, 1078, 1055, 1100, 1117, 1122, 1151, 1169, 1243, 1313, 1398, 1453, 1544, 1650 and 1725cm-1 provided excellent segregation of OSF spectra from normal using multivariate statistical techniques. These findings provided essential information on the metabolic features of blood serum of OSF patients and established that FTIR spectroscopy coupled with chemometric analysis can be potentially useful in the rapid and accurate preoperative screening/diagnosis of OSF.

"Omics" in oral cancer: New approaches for biomarker discovery.

OBJECTIVES: In this review paper, we explored the application of "omics" approaches in the study of oral cancer (OC). It will provide a better understanding of how "omics" approaches may lead to novel biomarker molecules or molecular signatures with potential value in clinical practice. A future direction of "omics"-driven research in OC is also discussed. METHODS: Studies on "omics"-based approaches [genomics/proteomics/transcriptomics/metabolomics] were investigated for differentiating oral squamous cell carcinoma,oral sub-mucous fibrosis, oral leukoplakia, oral lichen planus, oral erythroplakia from normal cases. Electronic databases viz., PubMed, Springer, and Google Scholar were searched. RESULTS: One eighty-one studies were included in this review. The review shows that the fields of genomics, transcriptomics, proteomics, and metabolomics-based marker identification have implemented advanced tools to screen early changes in DNA, RNA, protein, and metabolite expression in OC population. CONCLUSIONS: It may be concluded that despite advances in OC therapy, symptomatic presentation occurs at an advanced stage, where various curative treatment options become very limited. A molecular level study is essential for detecting an OC biomarker at an early stage. Modern "Omics" strategies can potentially make a major contribution to meet this need.