Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea.
Dig Endosc. 2023 Nov;35(7):918-926. doi: 10.1111/den.14648. Epub 2023 Aug 22.
Considering the critical roles of cancer-associated fibroblasts (CAFs) in pancreatic cancer, recent studies have attempted to incorporate stromal elements into organoid models to recapitulate the tumor microenvironment. This study aimed to evaluate the feasibility of patient-derived organoid (PDO) and CAF cultures by using single-pass endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples from prospectively enrolled pancreatic cancer patients. The obtained samples were split into two portions for PDO and CAF cultures. PDOs and CAFs were cultured successfully in 54.4% (31/57) and 47.4% (27/57) of the cases, respectively. Both components were established in 21 cases (36.8%). Various clinicopathologic factors, including the tumor size, tumor location, clinical stage, histologic subtype, and tumor differentiation, did not influence the PDO establishment. Instead, the presence of necrosis in tumor samples was associated with initial PDO generation but no further propagation beyond passage 5 (P = 0.024). The "poorly cohesive cell carcinoma pattern" also negatively influenced the PDO establishment (P = 0.018). Higher stromal proportion in tumor samples was a decisive factor for successful CAF culture (P = 0.005). Our study demonstrated that the coestablishment of PDOs and CAFs is feasible even with a single-pass EUS-FNB sample, implying an expanding role of endoscopists in future precision medicine.
考虑到癌症相关成纤维细胞(CAFs)在胰腺癌中的关键作用,最近的研究尝试将基质成分纳入类器官模型,以重现肿瘤微环境。本研究旨在评估通过前瞻性纳入的胰腺癌患者的单次经内镜超声引导细针活检(EUS-FNB)样本,建立患者来源的类器官(PDO)和 CAF 培养物的可行性。将获得的样本分为两部分用于 PDO 和 CAF 培养。分别有 54.4%(31/57)和 47.4%(27/57)的病例成功培养出 PDO 和 CAF。在 21 例(36.8%)中建立了这两种成分。各种临床病理因素,包括肿瘤大小、肿瘤位置、临床分期、组织学亚型和肿瘤分化,均不影响 PDO 的建立。相反,肿瘤样本中的坏死与初始 PDO 的产生相关,但在第 5 代以后无法进一步增殖(P=0.024)。“低黏附细胞癌模式”也对 PDO 的建立产生负面影响(P=0.018)。肿瘤样本中较高的基质比例是 CAF 培养成功的决定性因素(P=0.005)。我们的研究表明,即使使用单次 EUS-FNB 样本,也可以实现 PDO 和 CAF 的共同建立,这意味着内镜医生在未来的精准医学中发挥着更大的作用。