Chan Chia-Yi, Ni Yi-Chun, Nguyen Hieu Duc, Wu Yung-Fu, Lee Kuen-Haur
Department of Nursing, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Curr Issues Mol Biol. 2023 Sep 11;45(9):7417-7431. doi: 10.3390/cimb45090469.
Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.
尽管在过去几十年里进行了临床试验并引入了新的治疗方法,但卵巢癌仍然是全球女性中最致命的恶性肿瘤之一。基于铂类和紫杉醇的化疗对大多数卵巢癌患者有效。然而,超过70%的患者会复发并最终产生化疗耐药性。为了改善卵巢癌患者的临床结局,必须开发新技术来识别基于药物治疗卵巢癌后的分子改变。最近,细胞外囊泡(EVs)作为肿瘤进展的介质而备受关注。在本研究中,我们使用质谱法来识别由于用于治疗卵巢癌的不同化疗药物导致的EV蛋白质特征的变化。通过检查这些改变,我们确定了单独使用顺铂、单独使用紫杉醇以及顺铂和紫杉醇联合使用时的特定蛋白质诱导模式。具体而言,我们发现接受顺铂联合紫杉醇治疗的患者中,药物敏感性与膜联蛋白A5(ANXA5)、四跨膜蛋白81(CD81)和RAB5C的表达水平相关。我们的研究结果表明,化疗诱导的EV蛋白质特征变化对卵巢癌的进展至关重要。