Expression of transforming growth factor-β in oral submucous fibrosis: A systematic review

Oral submucous fibrosis (OSF) is a potentially malignant disorder characterised by inflammation and progressive fibrosis. Transforming growth factor-β (TGF-β) has been established as a master regulator of fibrosis in various organs; however, lack of systematic review on expression of TGF-β and its isoforms in OSF restrict the understanding of their behaviour in its pathogenesis. Online electronic databases, such as PubMed Medline, Cochrane Library, Embase, and Scopus, were searched from their respective dates of inception till 31st March 2022. Human studies related to TGF-β expression in histopathologically diagnosed OSF cases, with or without malignant transformation, were included and assessed using a Cochrane risk of bias assessment tool: For non randomised studies of interventions (ACROBAT NRSI). The electronic literature search yielded 394 articles. Of those, ten articles met the inclusion criteria and involved total of 579 OSF patients. The risk of bias (RoB) was low to moderate. These studies demonstrated a significant positive expression of TGF-β and its isoforms in OSF compared to that in normal tissue samples. An increased pan TGF-β expression was observed in the early stages of OSF, and an increased expression of TGF-β1 and TGF-β2 were seen in advanced stages of OSF. Stage wise expression of TGF-β3 has not been discussed in the included studies. No significant relationship was observed between epithelial dysplasia and TGF-β expression in OSF. The distinct pattern in the expression of pan TGF-β, TGF-β1 and TGF-β2 in various stages of OSF indicates their different roles in OSF progression. We believe isoform targeted studies exploring stage wise expression of the marker will open new treatment avenues for OSF.