Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer

Abstract

Ovarian cancer (OVCA) patients with suboptimal residual disease (RD) and advanced stages have poor survival. pGSN is an actin binding protein which protects OVCA cells from cisplatin-induced death. There is an urgent need to discover reliable biomarkers to optimize individualized treatment recommendations. 99 plasma samples with pre-determined CA125 were collected from OVCA patients and pGSN assayed using sandwich-based ELISA. Associations between CA125, pGSN and clinicopathological parameters were examined using Fisher’s exact test, T test and Kruskal Wallis Test. Univariate and multivariate Cox proportional hazard models were used to statistically analyze clinical outcomes. At 64 µg/ml, pGSN had sensitivity and specificity of 60% and 60% respectively, for the prediction of RD where as that of CA125 at 576.5 U/mL was 43.5% and 56.5% respectively. Patients with stage 1 tumor had increased levels of pre-operative pGSN compared to those with tumor stage >1 and healthy subjects (P = 0.005). At the value of 81 µg/mL, pGSN had a sensitivity and specificity of 75% and 78.4%, respectively for the detection of early stage OVCA. At the value of 0.133, the Indicator of Stage 1 OVCA (ISO1) provided a sensitivity of 100% at a specificity of 67% (AUC, 0.89; P < 0.001). In the multivariate Cox regression analysis, pGSN (HR, 2.00; CI, 0.99–4.05; P = 0.05) was an independent significant predictor of progression free survival (PFS) but not CA125 (HR, 0.68; CI, 0.41–1.13; P = 0.13). Pre-operative circulating pGSN is a favorable and independent biomarker for early disease detection, RD prediction and patients’ prognosis.

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

“…Importantly, plasma gelsolin is a powerful modulator of inflammation, which carries a protective function (DiNubile, 2008; Li et al, 2012). Low plasma gelsolin is a marker of poor prognosis in various pathological conditions, including diabetes (Khatri et al, 2014), cancers (Asare-Werehene et al, 2019; Stock et al, 2015) and sepsis (Lee et al, 2007), leading to suggestions and animal tests for its therapeutic use. Going forward, it will be important to assess GSN levels in at-risk populations for severe COVID-19, e.g.…”

Quantitative Serum Proteomics Reveals The Predictive and Prognostic Potential of Clusterin and Gelsolin in Head and Neck Squamous Cell Carcinoma Treated With Radiotherapy

“…In vitro studies in human oral carcinoma cells further elucidated the role of GSN in promoting apoptosis, cell proliferation, and enhancing tumor invasion and metastasis [44]. The ability of GSN to confer chemo-and radio-resistance has been reported in NSCLC, ovarian cancer, and HNSCC, all indicating that higher levels of GSN are associated with a higher risk of developing treatment resistance [17,18,45,46]. We report here, for the rst time, that the levels of GSN increase by 2.4 to 4.0 fold in the worst responding patients within 48 hours, which is maintained till 1 week of RT.…”

Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand

“…Asare-Werehene and colleagues [38] recently demonstrated that exosomal pGSN could promote the survival of ovarian cancer cells through both autocrine and paracrine stimulation and thereby confer chemoresistance. Moreover, preoperative circulating pGSN was found to be a favorable biomarker for early ovarian cancer detection, residual disease prediction, and overall prognosis [39]. Chen et al [40] also reported that serum pGSN levels were significantly lower in patients with colon cancer than in healthy controls and that pGSN could serve as a more effective diagnostic biomarker for colon cancer compared with the currently used carcinoembryonic antigen.…”