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

Abstract

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.

Soluble CD95L in cancers and chronic inflammatory disorders, a new therapeutic target?

“…However, the CD95L-expressing cells in the tumor tissue remains to be identified [90]. While oral squamous cell carcinoma showed no increase in s-CD95L when compared to healthy subjects [91], another study performed with head and neck cancers exhibited a significant reduction in s-CD95L compared to healthy subjects, indicating a different regulation of this ligand in these pathologies [92].…”

Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma

“…Gelsolin has also been found to be packaged into exosomes and secreted, termed plasma gelsolin (pGSN), with this form inhibiting CD8+-mediated tumor immune surveillance [50][51][52]. In this context, secreted gelsolin has been shown to inhibit neoantigen presentation to conventional dendritic cells in the tumor microenvironment, leading to immune evasion with a subsequent increase in glutathione (GSH) expression.…”

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

“…Signi cantly enhanced GSN expression was observed in oral squamous cell carcinoma (OSCC) and was associated with advanced staging [43]. Enzyme-linked immunosorbent assays (ELISA) of plasma samples indicated the potential of circulating plasma GSN as a diagnostic biomarker for head and neck cancer [14]. Immunohistochemical staining of laryngeal squamous cell carcinoma (LSCC) tissue samples indicated the association of GSN expression with poor prognosis and its potential as a novel prognostic biomarker for disease-speci c and overall survival [13].…”

“…HNSCC is a heterogeneous cancer, which makes the identi cation of a universal tissue biomarker di cult [8]. The role of tissue biomarkers in the diagnosis and prognosis of HNSCC has been studied [9], and elevated levels of proteins like clusterin (CLU) and gelsolin (GSN) have been reported in malignancies of the breast, bladder, prostrate, esophagus, and larynx [10][11][12][13][14]. CLU is an anti-apoptotic glycoprotein known to enhance tumorigenesis, with a possible role in the development of treatment-resistant phenotype [15,16].…”