Construction of a new tumor immunity-related signature to assess and classify the prognostic risk of ovarian cancer.

Ovarian cancer is associated with a high mortality rate. In this study, we established a new immune-related signature that can stratify ovarian cancer patients. First, we obtained immune-related genes through IMMUPORT, and DEGs (Differential Expression Genes) by analyzing the GSE26712 dataset. The APP (Antigen Processing and Presentation) and DEG signatures were established using univariate and multivariate Cox models. Kaplan-Meier analysis revealed the signatures' prognostic value in training and validation cohorts (HR: 0.379 VS. 0.450; 0.333 VS. 0.327). Nomogram analysis was used to assess the signatures' ability to predict the 30-month prognosis, which was evaluated using the calibration curve and time-dependent ROC curve (30-month AUC: 0.665 VS. 0.743). Time-dependent ROC, Decision Curve Analysis (DCA) and Integrated discrimination improvement (IDI) was used to compare the new model to previously published gene signatures. 30-month AUC composite variable (0.736) was higher than 9-gene signature (0.657), and composite variable had a larger net benefit and a higher IDI (+2.436%) relative to the 9-gene signature. Tumor immune infiltration and tumor microenvironment scores of the 2 groups separated by APP signature were compared. GSEA was used to identify enriched KEGG pathways. Conclusively, the proposed signature can stratify ovarian cancer patients by risk-score and guide clinical decisions.

An endogenous factor enhances ferulic acid decarboxylation catalyzed by phenolic acid decarboxylase from Candida guilliermondii.

The gene for a eukaryotic phenolic acid decarboxylase of Candida guilliermondii was cloned, sequenced, and expressed in Escherichia coli for the first time. The structural gene contained an open reading frame of 504 bp, corresponding to 168 amino acids with a calculated molecular mass of 19,828 Da. The deduced amino sequence exhibited low similarity to those of functional phenolic acid decarboxylases previously reported from bacteria with 25-39% identity and to those of PAD1 and FDC1 proteins from Saccharomyces cerevisiae with less than 14% identity. The C. guilliermondii phenolic acid decarboxylase converted the main substrates ferulic acid and p-coumaric acid to the respective corresponding products. Surprisingly, the ultrafiltrate (Mr 10,000-cut-off) of the cell-free extract of C. guilliermondii remarkably activated the ferulic acid decarboxylation by the purified enzyme, whereas it was almost without effect on the p-coumaric acid decarboxylation. Gel-filtration chromatography of the ultrafiltrate suggested that an endogenous amino thiol-like compound with a molecular weight greater than Mr 1,400 was responsible for the activation.

Purification and properties of phenolic acid decarboxylase from Candida guilliermondii.

A heat-labile phenolic acid decarboxylase from Candida guilliermondii (an anamorph of Pichia guilliermondii) was purified to homogeneity by simple successive column chromatography within 3 days. The molecular mass was 20 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 36 kDa by gel-filtration chromatography, suggesting that the purified enzyme is a homodimer. The optimal pH and temperature were approximately 6.0 and 25°C. Characteristically, more than 50% of the optimal activity was observed at 0°C, suggesting that this enzyme is cold-adapted. The enzyme converted p-coumaric acid, ferulic acid, and caffeic acid to corresponding products with high specific activities of approximately 600, 530, and 46 U/mg, respectively. The activity was stimulated by Mg(2+) ions, whereas it was completely inhibited by Fe(2+), Ni(2+), Cu(2+), Hg(2+), 4-chloromericuribenzoate, N-bromosuccinimide, and diethyl pyrocarbonate. The enzyme was inducible and expressed inside the cells moderately by ferulic acid and p-coumaric acid and significantly by non-metabolizable 6-hydroxy-2-naphthoic acid.