Aoife Ward Gahlawat

Potential of blood-based biomarker approaches in endometrium and breast cancer: a case-control comparison study

Abstract Purpose Endometrial carcinoma is the second most common gynecological malignancy. Until today lacking a screening tool. A blood-based biomarker could help address this need. Methods The expression levels of 30 acylcarnitines, 18 amino acids, 6 miRNAs, and 7 DNA methylation sites were measured in blood samples from 331 women (20 EC, 14 benign uterine lesions (benign), 140 breast cancers (BC), 157 controls). Areas under the ROC curves (AUC), sensitivity (sens.) and specificity (spec.) were computed to identify the variables best distinguishing. Results The best top ten markers for the four comparisons (cancer vs. cancer-free; EC vs. BC, EC vs. controls; EC vs. benign), were identified via AUC. Malonylcarnitine distinguished best patients with EC from controls (AUC: 0.827, sens. 80%, spec. 73.1%) or BC (AUC: 0.819, sens. 84.3%, spec. 80%) being most notable. Tryptophan best differentiated benign from EC (AUC: 0.846, sens. 70%, spec. 92.9%). Conclusions The levels of the analyzed blood markers yielded promising results in the detection of EC and warrant further evaluation.

Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer

AbstractOvarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years. Liquid biopsy markers have great potential to improve current diagnostic and prognostic methods. Here, we compared miRNAs and DNA methylation in matched plasma, whole blood and tissues as a surrogate marker for OC. We found that while both cfDNA and cf-miRNAs levels were upregulated in OC compared to patients with benign lesions or healthy controls, only cf-miRNA levels were an independent prognosticator of survival. Following on our previous work, we found members of the miR-200 family, miR-200c and miR-141 to be upregulated in both plasma and matched tissues of OC patients which correlated with adverse clinical features. We could also show that the upregulation of miR-200c and -141 correlated with promoter DNA hypomethylation in tissues, but not in plasma or matched whole blood samples. As cf-miRNAs are more easily obtained and very stable in blood, we conclude that they might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for OC.

A novel circulating miRNA panel for non-invasive ovarian cancer diagnosis and prognosis

AbstractBackgroundOvarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years after diagnosis. There is a pending need to improve current diagnostics and prognostics.MethodsIn this study, we investigated total circulating cell-free microRNA (cf-miRNA) levels as well as a panel of cf-miRNAs in the plasma of OC patients (n = 100), patients with benign lesions (n = 45) and healthy controls (n = 99).ResultsHigh levels of cf-miRNAs correlated with unfavourable clinical features and were an independent prognosticator of patient survival. By mining NGS data, we identified a signature panel of seven individual cf-miRNAs which could distinguish controls from benign cases with an AUC of 0.77 and controls from cancer cases with an AUC of 0.87. Importantly, in combination with the current gold-standard marker, CA-125, the panel could predict early OC with an AUC of 0.93.ConclusionOur findings highlight the potential of cf-miRNA levels as well as individual cf-miRNAs for OC diagnosis and prognosis that warrants further clinical evaluation.