Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.
Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.
复制标题
化疗后卵巢癌腹水衍生的肿瘤细胞的独特蛋白质组特征。
DOI：
10.1038/srep30061
复制
发表时间：
2016-07-29
影响因子：
4.6
通讯作者：
Kannourakis G
中科院分区：
文献类型：
--
作者：
Ahmed N;Greening D;Samardzija C;Escalona RM;Chen M;Findlay JK;Kannourakis G
80%的晚期卵巢癌患者在初次手术和化疗后完全缓解。然而，大多数患者在<5年内死亡，原因是残留的化疗耐药细胞的生长导致复发。为了确定与化疗耐药和复发相关的机制，我们通过使用深入的高分辨率无标记定量蛋白质组学分析，比较了从诊断时（chemonaive，CN）和化疗治疗后（chemoresistant/at recurrence，CR）的晚期卵巢癌患者中分离的腹水源性肿瘤细胞中蛋白质的表达。共鉴定出2,999种蛋白质。使用严格的选择标准，以确定只有显着差异表达的蛋白质，我们报告的353个蛋白质的鉴定。有显着差异的蛋白质编码的免疫监视，DNA修复机制，细胞骨架重排，细胞-细胞粘附，细胞周期途径，细胞转运，并参与甘氨酸/脯氨酸/精氨酸合成的蛋白质从CR相对CN患者分离的肿瘤细胞。途径分析显示CR肿瘤细胞中代谢途径、DNA修复机制和能量代谢途径的富集。总之，这是第一个全面分析CN和CR卵巢癌患者腹水源性肿瘤细胞的蛋白质组学研究。
Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients.