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Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of the actin-associated protein cytosolic gelsolin (GSN) regulates the gynecological cancer cell fate resulting in dysregulation in chemosensitivity. In this study, we report that elevated expression of plasma gelsolin (pGSN), a secreted isoform of GSN and expressed from the same GSN gene, correlates with poorer overall survival and relapse-free survival in patients with OVCA. In addition, it is highly expressed and secreted in chemoresistant OVCA cells than its chemosensitive counterparts. pGSN, secreted and transported via exosomes (Ex-pGSN), upregulates HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as confers cisplatin resistance in otherwise chemosensitive OVCA cells. These findings support our hypothesis that exosomal pGSN promotes OVCA cell survival through both autocrine and paracrine mechanisms that transform chemosensitive cells to resistant counterparts. Specifically, pGSN transported via exosomes is a determinant of chemoresistance in OVCA.

Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.