Abstract
Endometrial cancer (EC) is the fourth most abundant gynecological cancer. There is an increase in the incidence of mortality from uterine cancers in the past few decades. A comprehensive systematic study to provide an overview on the relationship between autophagy, metabolomics and the risk of oestradiol valerate (OV) induced endometrial cancer was conducted correlated with the use of liposomal loaded-resvida as an innovate drug delivery system. This article explores how metabolomic technology can offer valuable insights on autophagy molecular aspects in EC by identifying new possible metabolite biomarkers that has the potential to improve the accuracy of diagnosis, prognosis and disease monitoring. Metabolomics approach, included orthogonal partial least squares discriminant analysis (OPLS-DA), thus revolutionizes the management of endometrial cancer. Autophagy described in endometrial cancer, includes the role of HSP-70/C-fos/PTEN/mTOR/ERDj-4/p53 signaling pathways that trigger/inhibit the process and consequently represent a potential molecular targets in therapeutic approaches. Endometrial cancer exhibits a molecular complexity and heterogeneity coherent with histopathologic and metabolomic variability. Multivariate statistical analyses pointed out a noteworthy deviation in serum chemical profiles among control, oestradiol valerate, and Resvida and liposomal-Resvida treated groups. Loading plot guided the selection of differential metabolites, elucidating significant variation in metabolite concentration. Improved characterization of molecular alterations of each histological type provides relevant information about the prognosis and potential response to new liposomal therapies. CA125 as EC biomarker was ameliorated post Resvida (108.7 IU/mL) and liposomal Resvida (82.2 IU/Ml) treatment at P ≤ 0.05 in addition to up regulating autophagy biomarkers including mTOR/Cfos/ERDj-4/ PTEN by 20, 25, 14, and 17 fold change respectively and down regulating p53 protein expression by 0.4 ng/ml at P ≤ 0.05 post OV intoxication with liposomal regimen reflecting the most significant impact in modulating these altered genes. The current metabolomics study is the integration of histopathologic and autophagy molecular factors to improve the diagnosis, prognosis, and treatment of endometrial cancer in coherent with liposomal drug delivery system as a targeted therapy.
Keywords:
Autophagy markers; ERDj-4; Endometrial cancer; Metabolomics; mTOR.