Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment
Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment
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DOI：
10.1111/j.1349-7006.2009.01462.x
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发表时间：
2010-04-01
期刊：
影响因子：
5.7
通讯作者：
Shibata, Tatsuhiro
中科院分区：
文献类型：
--
作者：
Ojima, Hidenori;Yoshikawa, Daitaro;Shibata, Tatsuhiro
本研究的目的是建立新的胆道癌（BTC）细胞系并确定吉西他滨治疗潜在有效性的预测生物标志物。将BTC的手术标本直接移植到免疫缺陷小鼠体内建立异种移植物，然后进行体外细胞培养。确定每个细胞系的吉西他滨敏感性并与全基因组基因表达谱进行比较。使用另一组接受吉西他滨治疗的 BTC 病例对一种新的候选预测生物标志物进行了验证。从 55 个 BTC 病例中，我们建立了 19 个异种移植物和 6 个新细胞系。根据对吉西他滨的敏感性，将10个BTC细胞系（包括6个新的和4个公开的）明确分为两组，肿瘤细胞中MAGEH1 mRNA的表达与其对吉西他滨的敏感性呈显着负相关。免疫组织化学检测显示，六种敏感细胞系中的三种 (50%) 检测到了 MAGEH1 蛋白，四种耐药细胞系中的四种 (100%) 检测到了 MAGEH1 蛋白。在吉西他滨治疗的复发病例验证队列中，根据 RECIST 化疗效果评估指南将患者分为“有效”和“无效”组。在五个“有效”病例中的两个（40%）和所有四个（100%）“无效”病例中检测到 MAGEH1 蛋白表达。我们建立了一种新的BTC生物资源，涵盖了广泛的生物学特征，包括药物敏感性，并与临床信息相关联。 MAGEH1 蛋白的阴性表达可作为吉西他滨治疗 BTC 有效性的潜在预测标志物。 （癌症科学 2010 年；101：882-888）
The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into "effective'' and "non-effective'' groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five "effective'' cases and all four (100%) "non-effective'' cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC. (Cancer Sci 2010; 101: 882-888)