Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence.

OBJECTIVE: To investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. Methods Genome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4). RESULTS: A total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed. CONCLUSION: This study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC.

Semi-Automatic Prostate Segmentation From Ultrasound Images Using Machine Learning and Principal Curve Based on Interpretable Mathematical Model Expression.

Accurate prostate segmentation in transrectal ultrasound (TRUS) is a challenging problem due to the low contrast of TRUS images and the presence of imaging artifacts such as speckle and shadow regions. To address this issue, we propose a semi-automatic model termed Hybrid Segmentation Model (H-SegMod) for prostate Region of Interest (ROI) segmentation in TRUS images. H-SegMod contains two cascaded stages. The first stage is to obtain the vertices sequences based on an improved principal curve-based model, where a few radiologist-selected seed points are used as prior. The second stage is to find a map function for describing the smooth prostate contour based on an improved machine learning model. Experimental results show that our proposed model achieved superior segmentation results compared with several other state-of-the-art models, achieving an average Dice Similarity Coefficient (DSC), Jaccard Similarity Coefficient (Ω), and Accuracy (ACC) of 96.5%, 95.2%, and 96.3%, respectively.