Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization.

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-03-13 DOI:10.1038/s41598-025-93192-1

Rattanaporn Jaidee, Apinya Jusakul, Piman Pocasap, Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan, Watcharin Loilome, Attapol Titapun, Apiwat Jareanrat, Vasin Thanasukarn, Natcha Khuntikeo, Nisana Namwat, Yaovalux Chamgramol, Malinee Thanee, Phongsathorn Wichian, Jing Han Hong, Peiyong Guan, Hong Lee Heng, Chawalit Pairojkul, Bin Tean Teh, Sarinya Kongpetch

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引用次数: 0

Abstract

Cholangiocarcinoma (CCA) is a highly lethal hepatobiliary malignancy, with prognosis is influenced by anatomical subtypes and etiological factors. This study successfully established three CCA cell lines: KKU-097, KKU-466, and KKU-610, from the primary tumors of patients in liver fluke-endemic areas. These cells represent the perihilar CCA (pCCA) and intrahepatic CCA (iCCA) subtypes. Comprehensive analyses, including histopathology, molecular profiling, biomarkers, cancer phenotype characterization, and drug sensitivity testing with standard chemotherapeutics, were conducted. Whole-exome sequencing was performed to explore genetic alterations. All three cell lines exhibited adherent growth with an epithelial morphology and positive expression of the bile duct epithelial markers CK-7 and CK-19. Cytogenetic analysis revealed highly complex hypertriploid karyotypes with multiple chromosomal aberrations. Among the cell lines, KKU-610 demonstrated higher growth and invasion rates, whereas KKU-466 and KKU-097 cells exhibited less aggressive phenotypes. Drug sensitivity testing demonstrated relative resistance to gemcitabine as a monotherapy and in combination with cisplatin in all three cells. Genomic profiling identified targetable mutations, highlighting these new cell lines as valuable models for investigating the pathogenesis of CCA and evaluating therapeutic strategies.

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具有功能特征的胆管癌细胞的建立和基因组分析。

胆管癌（CCA）是一种高致死率的肝胆恶性肿瘤，其预后受解剖学亚型和病因的影响。本研究成功地从肝吸虫流行区患者的原发肿瘤中建立了3个CCA细胞系：KKU-097、KKU-466和KKU-610。这些细胞代表肝门周围CCA （pCCA）和肝内CCA （iCCA）亚型。综合分析，包括组织病理学、分子谱、生物标志物、癌症表型表征和标准化疗药物敏感性测试。进行全外显子组测序以探索遗传改变。所有三种细胞系均呈贴壁生长，具有上皮形态，胆管上皮标志物CK-7和CK-19表达阳性。细胞遗传学分析显示高度复杂的高三倍体核型与多个染色体畸变。在这些细胞系中，KKU-610细胞表现出较高的生长和侵袭率，而KKU-466和KKU-097细胞表现出较低的侵袭表型。药物敏感性试验显示，在所有三种细胞中，吉西他滨作为单一疗法和顺铂联合疗法相对耐药。基因组分析鉴定出靶向突变，强调这些新的细胞系是研究CCA发病机制和评估治疗策略的有价值的模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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