血漿型凝溶膠蛋白作為口腔癌生物標記物及其功能性角色

邱貞慈

doi:10.6844/NCKU202002731

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血漿型凝溶膠蛋白作為口腔癌生物標記物及其功能性角色

Plasma gelsolin as a biomarker of head and neck cancer and its functional roles

邱貞慈 , Ph.D　　Advisor：謝達斌　　

英文 DOI： 10.6844/NCKU202002731

血漿凝溶膠蛋白；細胞質凝溶膠蛋白；頭頸癌；細胞移動能力； plasma gelsolin ； cytosolic gelsolin ； head and neck cancer ； cell motility

Abstract │ Reference (89)

Abstract 〈TOP〉

Parallel Abstract 〈TOP〉

Gelsolin (GSN) is a multifunctional actin-binding protein that acts as a regulator of cell structure, motility and apoptosis. The two most abundant and well-known isoforms of GSN are plasma and cytosolic GSN (cGSN), plasma gelsolin (pGSN) differs from cGSN by an extended amino-terminal peptide which remains in mature protein after secretion. It has been reported that cGSN could predict disease progression in head and neck cancer (HNC) and other malignancies, while circulating pGSN levels significantly correlate with the prognosis of infectious and inflammatory diseases. In recent years, we discovered that cGSN modulates drug resistance in HNC through a common molecular signaling regulation. However, the potential roles of pGSN in cancer progression and prognosis remain elusive. In this study, the higher expression of pGSN in the medium of SCC25 was confirmed, which has a higher metastatic ability compared to HONE-1 cells. Our results showed that intracellular GSN protein levels were augmented in a dose-dependent manner upon exogenous pGSN-induction through integrin-dependent endocytosis. Furthermore, overexpression or knockdown of endogenous pGSN demonstrated the confident role of pGSN in epithelial-mesenchymal transition and migration as well as invasion of cells. These results suggested the role of pGSN in HNC to act as a tumor activity modulator. Besides, HNC ranks top ten causes of death in Taiwan, and the mortality increases considerably when the disease is diagnosed in its late stages. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. As one of the most abundant proteins in circulatory system and testified indicator of inflammation modulator, the pGSN may serve as a biomarker for HNC and as the predictor of patients’ clinical outcome. After screening 202 patients with HNC and 45 healthy controls, we 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. We conclude that pGSN not only plays a role in cancer migration and invasion, but also could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.

Reference ( 89 ) 〈TOP〉

Abedini, M. R., P. W. Wang, Y. F. Huang, M. Cao, C. Y. Chou, D. B. Shieh and B. K. Tsang (2014). "Cell fate regulation by gelsolin in human gynecologic cancers." Proc Natl Acad Sci USA. 111(40): 14442-14447.
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Asare-Werehene, M., L. Communal, E. Carmona, T. Le, D. Provencher, A. M. Mes-Masson and B. K. Tsang (2019). "Pre-operative circulating plasma gelsolin predicts residual disease and detects early stage ovarian cancer." Sci Rep. 9(1): 13924.
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