Chen Jiayu, Jin Ying, Li Siyi, Qiao Cui, Peng Xinxin, Li Yan, Gu Yu, Wang Wei, You Yan, Yin Jie, Shan Ying, Wang Yong-Xue, Qin Meng, Li Hongyue, Cai Yan, Dong Yu, Peng Siying, Pan Lingya
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China.
Front Oncol. 2021 Oct 4;11:744256. doi: 10.3389/fonc.2021.744256. eCollection 2021.
To generate robust patient-derived xenograft (PDX) models for epithelial ovarian cancer (EOC), analyze the resemblance of PDX models to the original tumors, and explore factors affecting engraftment rates, fresh cancer tissues from a consecutive cohort of 158 patients with EOC were collected to construct subcutaneous PDX models. Paired samples of original tumors and PDX tumors were compared at the genome, transcriptome, protein levels, and the platinum-based chemotherapy response was evaluated to ensure the reliability of the PDXs. Univariate and multivariate analyses were used to determine the factors affecting the engraftment rates. The engraftment success rate was 58.23% (92/158) over 3-6 months. The Ki-67 index and receiving neoadjuvant chemotherapy can affect the engraftment rate in primary patients. The PDX models generated in this study were found to retain the histomorphology, protein expression, and genetic alteration patterns of the original tumors, despite the transcriptomic differences observed. Clinically, the PDX models demonstrated a high degree of similarity with patients in terms of the chemotherapy response and could predict prognosis. Thus, the PDX model can be considered a promising and reliable preclinical tool for personalized and precise treatment.
为生成用于上皮性卵巢癌(EOC)的强大的患者来源异种移植(PDX)模型,分析PDX模型与原发肿瘤的相似性,并探索影响移植率的因素,收集了连续158例EOC患者的新鲜癌组织以构建皮下PDX模型。在基因组、转录组、蛋白质水平上比较原发肿瘤和PDX肿瘤的配对样本,并评估铂类化疗反应以确保PDX模型的可靠性。采用单因素和多因素分析来确定影响移植率的因素。在3至6个月内,移植成功率为58.23%(92/158)。Ki-67指数和接受新辅助化疗会影响初治患者的移植率。尽管观察到转录组差异,但本研究中生成的PDX模型被发现保留了原发肿瘤的组织形态学、蛋白质表达和基因改变模式。临床上,PDX模型在化疗反应方面与患者表现出高度相似性,并且可以预测预后。因此,PDX模型可被认为是一种用于个性化精准治疗的有前景且可靠的临床前工具。