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卵巢癌患者来源异种移植模型的建立及其影响因素分析

Establishment of patient-derived xenograft model in ovarian cancer and its influence factors analysis.

作者信息

Wu Jianfa, Zheng Yunxi, Tian Qi, Yao Ming, Yi Xiaofang

机构信息

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China.

出版信息

J Obstet Gynaecol Res. 2019 Oct;45(10):2062-2073. doi: 10.1111/jog.14054. Epub 2019 Aug 5.

Abstract

AIM

Patient-derived xenograft (PDX) model has been applied to the study of breast cancer, lung cancer, colon cancer and other cancers. However, its feasibility in ovarian cancer has not been understood. This study aimed to establish ovarian cancer PDX model and reveal its influence factors.

METHODS

In this study, 27 patients in Obstetrics and Gynecology Hospital affiliated to Fudan University from May 2015 to May 2016 were employed to explore the method of PDX model in ovarian cancer and verify its feasibility.

RESULTS

Finally, five cases of PDX models were successfully established, and the tumor formation rate (TFR) was 18.52%. In addition, immunohistochemistry and transcriptome sequencing analysis showed that tumor of PDX model have similar gene expression, gene splicing, gene fusion and single nucleotide polymorphisms with primary tumor (R = 0.741). Furthermore, it was revealed that compared to epithelial ovarian cancer, the TFR of PDX models with nonepithelial ovarian cancer was higher, while other factors such as the initiation site of tumor, the degree of tumor malignancy, the stage of tumor, the type of tumor and the species of experimental animals were not associated with the TFR.

CONCLUSION

Ovarian cancer PDX model, as a new scientific research model, can better keep the biological characteristics of primary tumor, which has great research value in ovarian cancer.

摘要

目的

患者来源的异种移植(PDX)模型已应用于乳腺癌、肺癌、结肠癌等癌症的研究。然而,其在卵巢癌中的可行性尚不清楚。本研究旨在建立卵巢癌PDX模型并揭示其影响因素。

方法

本研究选取2015年5月至2016年5月复旦大学附属妇产科医院的27例患者,探索卵巢癌PDX模型的构建方法并验证其可行性。

结果

最终成功建立了5例PDX模型,肿瘤形成率(TFR)为18.52%。此外,免疫组织化学和转录组测序分析表明,PDX模型的肿瘤与原发肿瘤在基因表达、基因剪接、基因融合和单核苷酸多态性方面具有相似性(R = 0.741)。此外,研究发现,与上皮性卵巢癌相比,非上皮性卵巢癌PDX模型的TFR更高,而肿瘤起始部位、肿瘤恶性程度、肿瘤分期、肿瘤类型和实验动物种类等其他因素与TFR无关。

结论

卵巢癌PDX模型作为一种新的科研模型,能够较好地保留原发肿瘤的生物学特性,在卵巢癌研究中具有重要的研究价值。

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