Establishing the role of transforming growth factor beta regulator 4 in cancer progression: A systematic review

Cancer is a term that evokes global concern which extends beyond a single disease entity claiming 9.7 million lives with incidence of 20 million per year. Transforming Growth Factor-β Regulator 4 (TBRG4), a mitochondrial regulatory protein, has recently emerged as a molecule of interest in several malignancies. Growing evidence also highlights its involvement in carcinomas such as hepatocellular carcinoma (HCC), lung cancer, breast cancer, and oral squamous cell carcinoma (OSCC), where altered expression of TBRG4 has been associated with cancer progression. Therefore, the current study aimed to systematically review the role of TBRG4 in cancer progression. PROSPERO registration preceded the strategic searching of electronic databases MEDLINE via PubMed, Cochrane Central, Embase, and Google Scholar. Upon comprehensive full-text assessment, ten articles meeting inclusion criteria were incorporated. ROBINS-E and QUIPS tools were used for quality assessment. In majority of the studies, TBRG4 expression-at both mRNA and protein levels was elevated in tumour tissues relative to adjacent normal tissues across multiple cancer types. Statistically significant correlations were, observed between TBRG4 expression and advanced clinical stages (III and IV) of OSCC, as well as with high histological grade (IV) and advanced tumour stages (T3 and T4) of HCC. This systematic review demonstrates that TBRG4 is closely associated with tumour progression, poor differentiation, therapeutic resistance, and diminished survival outcomes across various malignancies. These insights suggest the potential role of TBRG4 serving not only as a diagnostic adjunct (early lesion stratification in oral premalignant lesion such as leukoplakia), but also as a prognostic indicator (in OSCC and HCC), a predictive biomarker (for pharmacological response in Colorectal Cancer), and possibly as a therapeutic target.