Zuo Wei-Wei, Zhao Chun-Fang, Li Yan, Sun Hai-Yan, Ma Guo-Ming, Liu Yue-Ping, Kang Shan
Department of Gynecology, Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Gynecology, Tangshan People's Hospital, Tangshan, China.
Front Oncol. 2022 Jul 7;12:931445. doi: 10.3389/fonc.2022.931445. eCollection 2022.
This study aimed to explore the roles of PARP1 mRNA and protein expression in platinum resistance and prognosis of EOC patients, and reveal the different roles of PARP1 protein in epithelial tumor and stroma cells.
The mRNA expression of the EOC tissues was examined by RT-qPCR. The impacts of expression on prognosis were measured by Kaplan-Meier and Cox regression. Receiver operating characteristic (ROC) curve analysis was employed for calculating the diagnostic value of on platinum resistance. The microarray of formalin-fixed, paraffin-embedded (FFPE) tissues was processed for multiplex immunofluorescence to detect the protein levels of PARP1 and cytokeratin (CK).
The mRNA expression of EOC patients was higher in the platinum-resistant group compared with the sensitive group (P<0.01). Kaplan-Meier analysis demonstrated that high mRNA expression was associated with poor survival of EOC patients. In Cox regression analyses, high mRNA expression independently predicted poor prognosis (P=0.001, HR=2.076, 95%CI=1.373-3.140). The area under the ROC curve of mRNA for predicting the platinum resistance in EOC patients was 0.649, with a sensitivity of 0.607 and specificity of 0.668. Furthermore, the protein expression of was higher in the platinum-resistant group than in the sensitive group (P<0.01) and associated with a worse prognosis. Additionally, according to CK labeling, we observed that enhanced expression of in the CK+ region was associated with platinum resistance and lower survival, but in CK- region, it predicted a good prognosis and platinum sensitivity.
may be a potential biomarker to predict platinum resistance and prognosis for EOC patients, exerting different roles on epithelial tumor and stromal cells.
本研究旨在探讨PARP1 mRNA和蛋白表达在卵巢上皮性癌（EOC）患者铂耐药及预后中的作用，并揭示PARP1蛋白在上皮肿瘤细胞和基质细胞中的不同作用。
采用逆转录定量聚合酶链反应（RT-qPCR）检测EOC组织的mRNA表达。通过Kaplan-Meier法和Cox回归分析评估其表达对预后的影响。采用受试者工作特征（ROC）曲线分析计算其对铂耐药的诊断价值。对福尔马林固定、石蜡包埋（FFPE）组织进行微阵列多重免疫荧光检测，以检测PARP1和细胞角蛋白（CK）的蛋白水平。
与铂敏感组相比，铂耐药组EOC患者的mRNA表达更高（P<0.01）。Kaplan-Meier分析表明，高mRNA表达与EOC患者的不良生存相关。在Cox回归分析中，高mRNA表达独立预测不良预后（P=0.001，HR=2.076，95%CI=1.373-3.140）。预测EOC患者铂耐药的mRNA的ROC曲线下面积为0.649，灵敏度为0.607，特异性为0.668。此外，铂耐药组的蛋白表达高于敏感组（P<0.01），且与较差的预后相关。此外，根据CK标记，我们观察到CK+区域中PARP1表达增强与铂耐药和较低生存率相关，但在CK-区域，它预测预后良好和铂敏感。
PARP1可能是预测EOC患者铂耐药和预后的潜在生物标志物，在上皮肿瘤细胞和基质细胞中发挥不同作用。
