Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids.
Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids.
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人源性肝外胆道癌类器官的建立及药物筛选
DOI：
10.1186/s12935-021-02219-w
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发表时间：
2021-10-02
影响因子：
5.8
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Wang Z;Guo Y;Jin Y;Zhang X;Geng H;Xie G;Ye D;Yu Y;Liu D;Zhou D;Li B;Luo Y;Peng S;Li J
背景患者源性类器官（PDO）已被提出作为一种针对不同类型癌症进行药物筛选的新型体外方法。然而，迄今为止，肝外胆道癌（eBTC）PDO尚未完全established.MethodsWe收集了6个样本的胆囊癌（GBC）和一个样本的肝外胆管癌（eCCA）从7例患者试图建立eBTC PDO的药物筛选。我们成功建立了五个GBC和一个eCCA PDO。组织学染色用于比较原始组织和癌PDO之间的结构特征。进行全外显子组测序（WES）以分析原始组织和癌症PDO的遗传谱。药物筛选，包括吉西他滨，5-氟尿嘧啶，顺铂，紫杉醇，infigratinib，和ivosidenib，测量和验证的临床效果在某些cases.ResultsDifferent PDO在体外培养过程中表现出不同的生长速度。苏木精-伊红染色显示绝大多数癌性PDO的结构保留了腺癌的原有结构。免疫组化和高碘酸希夫染色显示，标志物表达在癌PDO是类似的原始标本。使用全外显子组测序分析来自四个原始样本以及配对癌症PDO的遗传图谱。四个PDO中的三个表现出高度的相似性时，与原始标本相比，除了GBC 2 PDO，其编码序列中的单核苷酸多态性的比例只有74%的一致性。一般来说，吉西他滨被认为是eBTC治疗的最有效药物，因为它对癌症生长显示出中度或显著的抑制作用。三个临床病例在一定程度上证实了药物筛选的结果。ConclusionsOur study successfully established a series of eBTC PDO，这为eBTC PDO领域做出了贡献。应探索其他增强措施，以提高PDO的生长速度并保护其免疫微环境。
BackgroundPatient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established.MethodsWe collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases.ResultsDifferent PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases.ConclusionsOur study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.
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影响因子：
2.4
作者：
Tantau AI;Mandrutiu A;Pop A;Zaharie RD;Crisan D;Preda CM;Tantau M;Mercea V
通讯作者：
Mercea V
影响因子：
64.5
作者：
Lee SH;Hu W;Matulay JT;Silva MV;Owczarek TB;Kim K;Chua CW;Barlow LJ;Kandoth C;Williams AB;Bergren SK;Pietzak EJ;Anderson CB;Benson MC;Coleman JA;Taylor BS;Abate-Shen C;McKiernan JM;Al-Ahmadie H;Solit DB;Shen MM
通讯作者：
Shen MM
影响因子：
25.7
作者：
Montal R;Sia D;Montironi C;Leow WQ;Esteban-Fabró R;Pinyol R;Torres-Martin M;Bassaganyas L;Moeini A;Peix J;Cabellos L;Maeda M;Villacorta-Martin C;Tabrizian P;Rodriguez-Carunchio L;Castellano G;Sempoux C;Minguez B;Pawlik TM;Labgaa I;Roberts LR;Sole M;Fiel MI;Thung S;Fuster J;Roayaie S;Villanueva A;Schwartz M;Llovet JM
通讯作者：
Llovet JM
影响因子：
8.8
作者：
Pape J;Magdeldin T;Stamati K;Nyga A;Loizidou M;Emberton M;Cheema U
通讯作者：
Cheema U
影响因子：
64.5
作者：
Neal, James T.;Li, Xingnan;Kuo, Calvin J.
通讯作者：
Kuo, Calvin J.