The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening.

miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Epi-genetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. The results demonstrate that the molecular constituents of BQs vary geographically and suggest that the differential disease-inducing capacity of BQs may reflect their distinct chemical composition. In summary, this was the first metabolomic study of BQs using GC–MS. Areca nut, husk, betel leaf, the inflorescence stem, and BQ mixture expressed distinctive metabolite patterns, and a significant variation in the content and concentration of metabolites was found across different geographical regions. Terpenes were mostly detected in betel leaves and inflorescence/stem. Safrole, a potentially genotoxic benzenoid, was found abundantly in betel (Piper betle) inflorescence from West Papua and was not detected in areca nut samples from any Indonesian region except West Papua.

These included mainly benzenoids and terpenes, as well as acids, aldehydes, alcohols, and esters. In addition to well-known alkaloids, the analysis of small-molecule profiles tentatively identified 92 phytochemicals in BQ. Here, we profiled for the first time the metabolomics of BQ constituents from four regions of Indonesia using non-targeted gas chromatography–mass spectrometry (GC–MS) analysis. We have recently shown that phenolic and alkaloid content of Indonesian BQs exhibits distinct geographical differences. Indonesia is one of the largest producers of areca nuts worldwide, yet little is known about the biomolecular composition of Indonesian areca nuts and BQs. Subsequently, IGF-I can be used as a marker for early detection of malignancy in oral premalignant lesions.oral premalignant conditions, like lichen planus, submucous fibrosis, leukoplakia, and erythroplakia, the levels of the IGF-I hormone are increased. IGF-I, through autophosphorylation of its receptor, activates the mitogen-activated protein kinases pathway that leads to the expression of IGF-I hormone. Insulin-like growth factor-I (IGF-I) is a peptide hormone with a structure similar to insulin and belongs to the family of growth factors that play a vital role in the development of embryonic, postembryonic, and normal physiological functions of the human body. Diabetic patients are frequently prone to developing oral health complications, such as being at a higher risk for developing oral precancerous conditions like lichen planus, leukoplakia, and erythroplakia. P>Diabetes mellitus is a disorder of the metabolic system that is diagnosed by hyperglycemia and glucose intolerance. Since myofibroblasts are involved in the malignant transformation of OSMF, the selective elimination of these cells will reduce the cancer development and ultimately the cancer burden. The detailed procedural aspects of this therapy along with experimental designs are also discussed. In the present paper, we propose that the adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein (FAP CAR T cell therapy) results in a significant reduction in fibrosis and restoration of function in OSMF. The myofibroblasts, which are associated with the malignant transformation express fibroblast-activating protein (FAP) on their surface that could be selectively targeted for the treatment of OSMF. The betel quid-associated chemicals, predominantly, arecoline and arecaidine, advance the activation of resident fibroblasts to myofibroblasts in OSMF, resulting in uncontrolled and excessive production of collagen.

This is attributed to the fact that any chronic fibrotic disease targeting myofibroblasts, the primary cells responsible for fibrosis is challenging. Despite several advancements in understanding the pathogenesis of oral submucous fibrosis (OSMF), there is no definitive therapy for the complete remission of the disease process.

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