Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel.

Biomarkers in cancer Pub Date : 2016-03-16 eCollection Date: 2016-01-01 DOI:10.4137/BIC.S35775
Urmila Sehrawat, Ruchika Pokhriyal, Ashish Kumar Gupta, Roopa Hariprasad, Mohd Imran Khan, Divya Gupta, Jasmine Naru, Sundararajan Baskar Singh, Ashok Kumar Mohanty, Perumal Vanamail, Lalit Kumar, Sunesh Kumar, Gururao Hariprasad
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Abstract

Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response.

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对晚期卵巢癌组织进行蛋白质组学比较分析,以确定卡铂和紫杉醇一线化疗应答者和非应答者的潜在生物标志物
晚期卵巢癌的传统治疗方法是先进行剥离手术,然后进行卡铂和紫杉醇联合化疗。尽管最初的反应较高,但这些妇女中有四分之三会复发,预后不佳。接受过细胞切除手术的晚期卵巢癌患者被纳入研究对象,并采集了组织样本。手术后,这些患者开始接受化疗,并随访至周期结束。实验的发现阶段采用了基于荧光的凝胶内差异表达和质谱分析,并对差异表达蛋白的表达和功能进行了实时聚合酶链反应、Western 印迹和通路分析验证。醛还原酶、hnRNP、环嗜蛋白 A、热休克蛋白-27 和肌动蛋白在应答者中上调,而禁止素、烯酰-coA 水合酶、过氧化物酶和纤维蛋白-β在非应答者中上调。其中一些蛋白质的表达与应答者的凋亡活性增加和非应答者的凋亡活性降低相关。因此,这些蛋白质可作为预测化疗反应的潜在生物标志物。
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