结直肠癌患者肿瘤类器官生物样本库在预测化疗效果中的应用研究

The study of predicting individual response to chemotherapy for colorectal cancer patients based on tumoroids living biobank

目的本研究通过建立结直肠癌(advanced colorectal cancer,CRC)患者来源的肿瘤类器官(tumoroid)生物样本库,于体外模拟CRC肿瘤组织的生物学行为,为肿瘤类器官作为临床前模型评估CRC患者化疗效果提供理论基础支持。方法收集CRC患者的肿瘤组织分离培养肿瘤类器官,对肿瘤类器官进行组织形态学评估;进一步以不同化疗方案药物处理肿瘤类器官,采用CellTiter-GIo 3D细胞活力检测试剂盒测定评估肿瘤类器官的药物敏感性,并与患者的临床疗效进行对比分析。结果肿瘤类器官经过连续传代后仍然与原始肿瘤组织形态学保持高度一致;不同患者来源的肿瘤类器官的药物敏感性与对应CRC患者临床疗效的一致性高达91.18%(31/34),肿瘤类器官的药物抑制率与CRC患者的无进展生存期(progression-free survival,PFS)呈正相关关系(rs=0.412,P=0.016),而肿瘤类器官细胞活性-药物浓度曲线下面积与CRC患者的PFS呈负相关关系(rs=–0.479,P=0.004)。结论本研究建立了CRC患者的肿瘤类器官生物样本库,且提示肿瘤类器官具有作为临床前实验模型及预判CRC患者化疗效果的潜能。

Objective In this study,we present a living biobank of patient-derived tumoroids from advanced colorectal cancer(CRC)patients and show examples of how these tumoroids can be used to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy to identify the chemotherapy response.Methods The tumor tissues of CRC patients were collected to isolate and culture tumoroids,and the histomorphology of tumoroids was evaluated.Further,tumoroids were treated with drugs of different chemotherapy schemes,and the drug sensitivity of tumoroids was evaluated by using CellTiter-GIo 3D cell viability assay,and the clinical efficacy was compared with that of patients.Results The tumoroids were still highly consistent with the original tumor histomorphology after continuous passage.The consistency between the drug sensitivity of tumoroids from different patients and the clinical efficacy of corresponding CRC patients was 91.18%(31/34).The drug inhibition rate of tumoroids was positively correlated with the progression free survival(PFS)of CRC patients(rs=0.412,P=0.016),while the area under the cell activity drug concentration curve of tumoroids was negatively correlated with the PFS of CRC patients(rs=–0.479,P=0.004).Conclusion This study established a biological sample bank of tumoroids for CRC patients,and suggested that tumoroids had the potential to be used as preclinical experimental models and predict the chemotherapy effect of CRC patients.