Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Plasma glycoproteomic biomarkers identify metastatic melanoma patients with reduced clinical benefit from immune checkpoint inhibitor therapy.

The clinical success of immune-checkpoint inhibitors (ICI) in both resected and metastatic melanoma has confirmed the validity of therapeutic strategies that boost the immune system to counteract cancer. However, half of patients with metastatic disease treated with even the most aggressive regimen do not derive durable clinical benefit. Thus, there is a critical need for predictive biomarkers that can identify individuals who are unlikely to benefit with high accuracy so that these patients may be spared the toxicity of treatment without the likely benefit of response. Ideally, such an assay would have a fast turnaround time and minimal invasiveness. Here, we utilize a novel platform that combines mass spectrometry with an artificial intelligence-based data processing engine to interrogate the blood glycoproteome in melanoma patients before receiving ICI therapy. We identify 143 biomarkers that demonstrate a difference in expression between the patients who died within six months of starting ICI treatment and those who remained progression-free for three years. We then develop a glycoproteomic classifier that predicts benefit of immunotherapy (HR=2.7; p=0.026) and achieves a significant separation of patients in an independent cohort (HR=5.6; p=0.027). To understand how circulating glycoproteins may affect efficacy of treatment, we analyze the differences in glycosylation structure and discover a fucosylation signature in patients with shorter overall survival (OS). We then develop a fucosylation-based model that effectively stratifies patients (HR=3.5; p=0.0066). Together, our data demonstrate the utility of plasma glycoproteomics for biomarker discovery and prediction of ICI benefit in patients with metastatic melanoma and suggest that protein fucosylation may be a determinant of anti-tumor immunity.

Mental Health and Health Risk Behaviors of Active Duty Sexual Minority and Transgender Service Members in the United States Military.

Purpose: The aim of this study was to examine health risk behaviors and mental health outcomes among sexual minority and transgender active duty military service members and their heterosexual and cisgender counterparts. Methods: Participants (N = 544) were recruited by using respondent-driven sampling between August 2017 and March 2018 and completed an online survey by using validated measures of cigarette smoking, alcohol use, anxiety, depression, post-traumatic stress disorder (PTSD), and suicidality. Bayesian random intercept multiple logistic regressions were used to understand differences between sexual minority participants and heterosexual participants as well as between transgender participants and both their cisgender sexual minority and cisgender heterosexual peers. Results: Cisgender sexual minority women service members were more likely to meet criteria for problematic alcohol use (adjusted odds ratio [aOR] = 10.11) and cigarette smoking (aOR = 7.12) than cisgender heterosexual women. Cisgender sexual minority men had greater odds of suicidality (aOR = 4.73) than their cisgender heterosexual counterparts. Transgender service members had greater odds of anxiety, PTSD, depression, and suicidality than their cisgender peers. Conclusion: Military researchers and policymakers who seek to improve the overall health and well-being of sexual minority and transgender service members should consider programs and policies that are tailored to specific health outcomes and unique sexual minority and transgender subgroups.