利用患者源性类器官实现个性化肝癌治疗
Leveraging Patient-Derived Organoids for Personalized Liver Cancer Treatment
DOI 原文链接
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影响因子:10
分区:生物学1区 Top / 生化与分子生物学2区
发表日期:2024
作者:
Jianhua Rao, Chao Song, Yangyang Hao, Zaozao Chen, Sidu Feng, Shihui Xu, Xiaoyue Wu, Zhengfeng Xuan, Ye Fan, Wenzhu Li, Junda Li, Yong Ren, Jian Li, Feng Cheng, Zhongze Gu
DOI:
10.7150/ijbs.96317
摘要
原发性肝癌（PLC）是全球癌症相关死亡的主要原因之一，由于治疗选择有限和肿瘤异质性，亟需新型治疗方法。通过自研的2:2培养方法，培养了66例手术切除的PLC样本，最终类器官培养成功率为40.9%。利用全外显子测序、RNA测序以及抗癌药物测试等综合分子检测方法对类器官性能进行了评估。多种类器官及其对应的肿瘤组织均含有多种相同突变，所有配对样本均共享常见的TP53突变。在拷贝数变异和基因表达方面，观察到类器官与其对应的肿瘤组织之间存在显著的相关性。分子水平的比较为类器官与肿瘤的符合程度提供了评估，结合药物敏感性测试，为治疗方案的制定提供了直接指导。最终，我们为一例ICC患者确定了合适的药物方案，展示了个体化药物方案的临床实用性。本研究提供了一种能保持肿瘤大部分分子特征、用于药物敏感性测试的类器官培养技术，展示了类器官技术在肝癌精准治疗中的广泛潜在应用。
Abstract
Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%. Organoid performance has been evaluated using comprehensive molecular measurements, such as whole-exome and RNA sequencing, as well as anticancer drug testing. Multiple organoids and their corresponding tumor tissues contained several of the same mutations, with all pairs sharing conventional TP53 mutations. Regarding copy number variations and gene expression, significant correlations were observed between the organoids and their corresponding parental tumor tissues. Comparisons at the molecular level provided us with an assessment of organoid-to-tumor concordance, which, in combination with drug sensitivity testing provided direct guidance for treatment selection. Finally, we were able to determine an appropriate pharmacological regimen for a patient with ICC, demonstrating the clinical practicality in tailoring patient-specific drug regimens. Our study provides an organoid culture technology that can cultivate models that retain most of the molecular characteristics of tumors and can be used for drug sensitivity testing, demonstrating the broad potential application of organoid technology in precision medicine for liver cancer treatment.