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Objective: Nuanced distress screening tools can help cancer care services manage specific cancer groups' concerns more efficiently. This study examines the sensitivity and specificity of a tool specifically for women with gynaecological cancers (called the Gynaecological Cancer Distress Screen or DT‐Gyn). Methods: This paper presents cross‐sectional data from individuals recently treated for gynaecological cancer recruited through Australian cancer care services, partner organisations, and support/advocacy services. Receiver operating characteristics analyses were used to evaluate the diagnostic accuracy of the DT‐Gyn against criterion measures for anxiety (GAD‐7), depression (patient health questionnaire), and distress (IES‐R and K10). Results: Overall, 373 individuals aged 19–91 provided complete data for the study. Using the recognised distress thermometer (DT) cut‐off of 4, 47% of participants were classified as distressed, while a cut‐off of 5 suggested that 40% had clinically relevant distress. The DT‐Gyn showed good discriminant ability across all measures (IES‐R: area under the curve (AUC) = 0.86, 95% CI = 0.82–0.90; GAD‐7: AUC = 0.89, 95% CI = 0.85–0.93; K10: AUC = 0.88, 95% CI = 0.85–0.92; PHQ‐9: AUC = 0.85, 95% CI = 0.81–0.89) and the Youden Index suggested an optimum DT cut‐point of 5. Conclusions: This study established the psychometric properties of the DT‐Gyn, a tool designed to identify and manage the common sources of distress in women with gynaecological cancers. We suggest a DT cut point ≥5 is optimal in detecting 'clinically relevant' distress, anxiety, and depression in this population. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), including exosomes, have significant potential for diagnostic and therapeutic applications. The lack of standardized methods for efficient and high-throughput isolation and analysis of EVs, however, has limited their widespread use in clinical practice. Surface epitope immunoaffinity (SEI) isolation utilizes affinity ligands, including antibodies, aptamers, or lectins, that target specific surface proteins present on EVs. Paramagnetic bead-SEI isolation represents a fit-for-purpose solution for the reproducible, high-throughput isolation of EVs from biofluids and downstream analysis of RNA, protein, and lipid biomarkers that is compatible with clinical laboratory workflows. This study evaluates a new SEI isolation method for enriching subpopulations of EVs. EVs were isolated from human plasma using a bead-based SEI method designed for on-bead and downstream analysis of EV-associated RNA and protein biomarkers. Western blot analysis confirmed the presence of EV markers in the captured nanoparticles. Mass spectrometry analysis of the SEI lysate identified over 1500 proteins, with the top 100 including known EV-associated proteins. microRNA (miRNA) sequencing followed by RT-qPCR analysis identified EV-associated miRNA transcripts. Using SEI, EVs were isolated using automated high-throughput particle moving instruments, demonstrating equal or higher protein and miRNA yield and recovery compared to manual processing. SEI is a rapid, efficient, and high-throughput method for isolating enriched populations of EVs; effectively reducing contamination and enabling the isolation of a specific subpopulation of EVs. In this study, high-throughput EV isolation and RNA extraction have been successfully implemented. This technology holds great promise for advancing the field of EV research and facilitating their application for biomarker discovery and clinical research., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: This study aimed to identify serum glycoprotein biomarkers for early detection of high-grade serous ovarian cancer (HGSOC), the most common and aggressive histotype of ovarian cancer., Experimental Design: The glycoproteomics pipeline lectin magnetic bead array (LeMBA)-mass spectrometry (MS) was used in age-matched case-control serum samples. Clinical samples collected at diagnosis were divided into discovery (n = 30) and validation (n = 98) sets. We also analysed a set of preclinical sera (n = 30) collected prior to HGSOC diagnosis in the UK Collaborative Trial of Ovarian Cancer Screening., Results: A 7-lectin LeMBA-MS/MS discovery screen shortlisted 59 candidate proteins and three lectins. Validation analysis using 3-lectin LeMBA-multiple reaction monitoring (MRM) confirmed elevated A1AT, AACT, CO9, HPT and ITIH3 and reduced A2MG, ALS, IBP3 and PON1 glycoforms in HGSOC. The best performing multimarker signature had 87.7% area under the receiver operating curve, 90.7% specificity and 70.4% sensitivity for distinguishing HGSOC from benign and healthy groups. In the preclinical set, CO9, ITIH3 and A2MG glycoforms were altered in samples collected 11.1 ± 5.1 months prior to HGSOC diagnosis, suggesting potential for early detection., Conclusions and Clinical Relevance: Our findings provide evidence of candidate early HGSOC serum glycoprotein biomarkers, laying the foundation for further study in larger cohorts., (© 2023 The Authors. Proteomics - Clinical Applications published by Wiley-VCH GmbH.)