Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors

Objective. To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods. In this exploratory diagnostic study, 254 patientswith an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. Results. CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. Conclusions. The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.status: accepte

Identification and Quantification of Dityrosine in Grain Proteins by Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry

A novel liquid chromatography-tandem mass spectrometry method was developed and validated for identification and quantification of dityrosine in zein protein. The zein samples spiked with a dityrosine standard and 3,3-13C6-dityrosine, as the internal standard were hydrolysed in a mixture of 6 N hydrochloric acid and propionic acid followed by cleaning-up using Sep Pak C18 cartridges. Good linear regression (R2 = 0.999) was obtained in the range 1–1000 ng/mL. Method limit of detection and method limit of quantification were 42.1 and 140 ng/g, respectively. Recoveries were from 92 to 95.2%. Precision and inter-day reproducibility expressed as relative standard deviation were from 3.9 to 22.1% and from 4.4 to 16.6%, respectively. The validated method was applied to quantify dityrosine in various grain proteins. The levels of dityrosine ranged from 0.38 to 1.92 ng/mg. This validated method will be of great value for understanding the role of dityrosine in grain food texture

Covariation and phenotypic integration in chemical communication displays: biosynthetic constraints and eco-evolutionary implications

Chemical communication is ubiquitous. The identification of conserved structural elements in visual and acoustic communication is well established, but comparable information on chemical communication displays (CCDs) is lacking. We assessed the phenotypic integration of CCDs in a meta‐analysis to characterize patterns of covariation in CCDs and identified functional or biosynthetically constrained modules. Poorly integrated plant CCDs (i.e. low covariation between scent compounds) support the notion that plants often utilize one or few key compounds to repel antagonists or to attract pollinators and enemies of herbivores. Animal CCDs (mostly insect pheromones) were usually more integrated than those of plants (i.e. stronger covariation), suggesting that animals communicate via fixed proportions among compounds. Both plant and animal CCDs were composed of modules, which are groups of strongly covarying compounds. Biosynthetic similarity of compounds revealed biosynthetic constraints in the covariation patterns of plant CCDs. We provide a novel perspective on chemical communication and a basis for future investigations on structural properties of CCDs. This will facilitate identifying modules and biosynthetic constraints that may affect the outcome of selection and thus provide a predictive framework for evolutionary trajectories of CCDs in plants and animals.The project was supported by the Graduate School ‘Evolutionary Networks: Organisms, Reactions, Molecules’ (E‐Norm) of the Heinrich‐Heine‐University, Düsseldorf, Germany, the Max Planck Society and the Deutsche Forschungsgemeinschaft (DFG JU 2856/1‐1 and DFG JU 2856/2‐2)