Purpose

Early dissemination of primary pancreatic ductal adenocarcinoma (PDAC) is the main cause of dismal prognosis as it highly limits possible treatment options. A number of PDAC patients experience distant metastasis even after treatment due to the metastatic clones. We aimed to demonstrate the molecular architecture of borderline resectable PDAC manifests cancer dissemination of PDAC.

Methods

Here, 36 organoids isolated from primary tumor masses of PDAC patients with diverse metastatic statues are presented. Whole-exome sequencing and RNA sequencing were performed and drug responses to clinically relevant 18 compounds were assessed.

Results

Our results revealed that borderline resectable PDAC organoids exhibited distinct patterns according to their metastatic potency highlighted by multiple genetic and transcriptional factors and strong variances in drug responses.

Conclusions

These data suggest that the presence of metastatic PDAC can be identified by integrating molecular compositions and drug responses of borderline resectable PDAC.

中文翻译：

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36 种胰腺癌类器官的建立、表征和生物库：预测可切除胰腺癌的转移

目的

原发性胰腺导管腺癌（PDAC）的早期传播是预后不良的主要原因，因为它极大地限制了可能的治疗选择。由于转移性克隆，许多 PDAC 患者即使在治疗后仍会出现远处转移。我们的目的是证明临界可切除 PDAC 的分子结构表明 PDAC 的癌症扩散。

方法

在此，展示了从具有不同转移状态的 PDAC 患者原发肿瘤块中分离出的 36 个类器官。进行了全外显子组测序和 RNA 测序，并评估了对临床相关 18 种化合物的药物反应。

结果

我们的结果显示，边缘可切除的 PDAC 类器官根据其转移效力表现出不同的模式，这些模式由多种遗传和转录因素以及药物反应的强烈差异所强调。

结论

这些数据表明，可以通过整合临界可切除 PDAC 的分子组成和药物反应来识别转移性 PDAC 的存在。