郑文瑾, 叶明侠, 王铭洋, 孟元光. 卵巢恶性肿瘤类器官库的初建[J]. 解放军医学院学报, 2024, 45(6): 631-637, 651. DOI: 10.12435/j.issn.2095-5227.2024.058
引用本文: 郑文瑾, 叶明侠, 王铭洋, 孟元光. 卵巢恶性肿瘤类器官库的初建[J]. 解放军医学院学报, 2024, 45(6): 631-637, 651. DOI: 10.12435/j.issn.2095-5227.2024.058
ZHENG Wenjin, YE Mingxia, WANG Mingyang, MENG Yuanguang. Establishment of an ovarian malignant tumor organoid biobank[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(6): 631-637, 651. DOI: 10.12435/j.issn.2095-5227.2024.058
Citation: ZHENG Wenjin, YE Mingxia, WANG Mingyang, MENG Yuanguang. Establishment of an ovarian malignant tumor organoid biobank[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(6): 631-637, 651. DOI: 10.12435/j.issn.2095-5227.2024.058

卵巢恶性肿瘤类器官库的初建

Establishment of an ovarian malignant tumor organoid biobank

  • 摘要:
    背景 卵巢恶性肿瘤异质性导致患者个体治疗效果差异大,经典治疗方案无法实现患者个体化治疗。可靠的卵巢恶性肿瘤体外模型可作为患者“替身”进行研究和药物敏感性测定,其结果为卵巢恶性肿瘤患者的精准治疗提供新思路。
    目的 建立卵巢恶性肿瘤类器官生物库,在基因组学层面验证类器官与对应卵巢癌组织的一致性,探索类器官模型药敏结果预测临床疗效的可行性。
    方法 分离患者组织来源的卵巢恶性肿瘤细胞,在基质胶三维环境中培养形成类器官。利用全外显子测序技术检测并对比类器官与对应卵巢恶性肿瘤组织的基因组学特征。类器官培养2 ~ 3 d后加入化疗单药或联合方案药物,进行药物敏感性测定。
    结果 本研究建立了卵巢恶性肿瘤类器官生物库,包含来自113例患者的122个类器官系,培养成功率达90.4%。全外显子测序分析显示卵巢恶性肿瘤类器官在基因组学层面与亲本肿瘤组织具有一致性。卵巢恶性肿瘤类器官药敏结果对临床疗效的预测准确性达70.7%,敏感度为75%,特异度为55.6%。
    结论 本研究在体外成功建立了卵巢恶性肿瘤类器官生物库,类器官模型可反映亲本肿瘤的基因组学特征,其药敏结果可反映临床疗效。卵巢恶性肿瘤类器官库为卵巢恶性肿瘤研究、药物开发、临床治疗方案制定提供了可靠的临床前模型。

     

    Abstract:
    Background The heterogeneity of ovarian malignant tumors leads to large differences in individual patient outcomes, and classical treatment protocols are unable to achieve individualized treatment. The in vitro model of ovarian malignancy can be used as a substitute for patients for research and drug sensitivity assays, and the results may provide new clues for precision treatment of patients with ovarian malignancy.
    Objective To establish a biobank of ovarian malignant tumor organoids, validate the consistency of the organoids with the corresponding ovarian cancer tissues at the genomic level, and explore the feasibility of predicting clinical efficacy with the drug sensitivity results of organoid models.
    Methods Ovarian malignant tumor cells derived from patient tissues were isolated and cultured in a matrigel 3D environment to form organoids. The genomic characteristics of the organoid and the corresponding ovarian malignant tumor tissues were detected and compared using whole-exome sequencing. The organoid was cultured for 2-3 days and then added to chemotherapeutic drug or drug combination regimen for drug sensitivity determination.
    Results A biobank of ovarian malignant tumor organoids was established in this study, containing 122 organoids from 113 patients, with a culture success rate of 90.4%. Whole-exome sequencing analysis showed that the ovarian malignant tumor organoids were consistent with the parental tumor tissues at the genomic level. The drug sensitivity results of ovarian malignant tumor organoids predicted clinical efficacy with an accuracy of 70.7%, a sensitivity of 75% and a specificity of 55.6%.
    Conclusion In this study, a biobank of ovarian malignant tumor organoids has been successfully established in vitro, and the organoid model can reflect the genomic characteristics of the parental tumor, and its drug sensitivity results can reflect the clinical efficacy. The ovarian malignant tumor organoid biobank provides a reliable preclinical model for ovarian malignant tumour research, drug development and clinical treatment protocol formulation.

     

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