The Application of an Extracellular Vesicle-Based Biosensor in Early Diagnosis and Prediction of Chemoresponsiveness in Ovarian Cancer

Meshach Asare-Werehene, Robert A. Hunter, Emma Gerber, Arkadiy Reunov, Isaiah Brine, Chia Yu Chang, Chia Ching Chang, Dar Bin Shieh, Dylan Burger, Hanan Anis, Benjamin K. Tsang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Background: Ovarian cancer (OVCA) is the most fatal gynecological cancer with late diagnosis and plasma gelsolin (pGSN)-mediated chemoresistance representing the main obstacles to treatment success. Since there is no reliable approach to diagnosing patients at an early stage as well as predicting chemoresponsiveness, there is an urgent need to develop a diagnostic platform for such purposes. Small extracellular vesicles (sEVs) are attractive biomarkers given their potential accuracy for targeting tumor sites. Methods: We have developed a novel biosensor which utilizes cysteine-functionalized gold nanoparticles that simultaneously bind to cisplatin (CDDP) and plasma/cell-derived EVs, affording us the advantage of predicting OVCA chemoresponsiveness, and early diagnosis using surface-enhanced Raman spectroscopy. Results: We found that pGSN regulates cortactin (CTTN) content resulting in the formation of nuclear- and cytoplasmic-dense granules facilitating the secretion of sEVs carrying CDDP; a strategy used by resistant cells to survive CDDP action. The clinical utility of the biosensor was tested and subsequently revealed that the sEV/CA125 ratio outperformed CA125 and sEV individually in predicting early stage, chemoresistance, residual disease, tumor recurrence, and patient survival. Conclusion: These findings highlight pGSN as a potential therapeutic target and provide a potential diagnostic platform to detect OVCA earlier and predict chemoresistance; an intervention that will positively impact patient-survival outcomes.

原文English
文章編號2566
期刊Cancers
15
發行號9
DOIs
出版狀態Published - 2023 5月

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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