Yu Jingwei, Gao Jing, Lu Zhihao, Gong Jifang, Li Yanyan, Dong Bin, Li Zhongwu, Zhang Xiaotian, Shen Lin
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Eur J Cancer. 2014 Sep;50(13):2328-35. doi: 10.1016/j.ejca.2014.06.017. Epub 2014 Jul 10.
To investigate the role of microtubule associated protein-tau (MAP-tau) and β-tubulin III (TUBB3) in predicting the chemosensitivity of paclitaxel in patients with advanced gastric cancer (GC).
MAP-tau and TUBB3 expressions were detected using immunohistochemistry in 244 advanced GC patients prior to chemotherapy. The associations of MAP-tau and TUBB3 expressions with paclitaxel sensitivity were assessed using in vitro and in vivo xenograft analysis.
A total of 149 patients receiving paclitaxel plus capecitabine (cohort 1) and 95 patients receiving cisplatin plus capecitabine (cohort 2) were included in this study. In cohort 1, the clinical benefit rate (CBR), median progression-free survival (PFS) and overall survival (OS) were found to be significantly higher in patients with low levels of MAP-tau and TUBB3 expressions and were significantly higher than those in patients with high levels of MAP-tau and TUBB3 expressions (CBR: 72.2% versus 35.9%; PFS: 271 versus 102 days; OS: 394 versus 173 days; all P<0.05). This was not observed in cohort 2. In in vitro studies, the sensitivity of paclitaxel in human gastric cancer cells was inversely correlated with the expression levels of MAP-tau and TUBB3, as in in vivo animal xenografts.
The combination of MAP-tau and TUBB3 was found to predict chemosensitivity to paclitaxel in gastric cancer in vitro and in vivo. This merits further study and may help guide individual therapy.
探讨微管相关蛋白tau（MAP-tau）和β-微管蛋白III（TUBB3）在预测晚期胃癌（GC）患者对紫杉醇化疗敏感性中的作用。
采用免疫组织化学法检测244例晚期GC患者化疗前的MAP-tau和TUBB3表达。通过体外和体内异种移植分析评估MAP-tau和TUBB3表达与紫杉醇敏感性的相关性。
本研究共纳入149例接受紫杉醇加卡培他滨治疗的患者（队列1）和95例接受顺铂加卡培他滨治疗的患者（队列2）。在队列1中，MAP-tau和TUBB3低表达患者的临床获益率（CBR）、中位无进展生存期（PFS）和总生存期（OS）显著高于MAP-tau和TUBB3高表达患者（CBR：72.2%对35.9%；PFS：271天对102天；OS：394天对173天；均P<0.05）。队列2未观察到这种情况。体外研究显示，人胃癌细胞对紫杉醇的敏感性与MAP-tau和TUBB3的表达水平呈负相关，体内动物异种移植实验结果与之相同。
发现MAP-tau和TUBB3的联合检测可在体外和体内预测胃癌对紫杉醇的化疗敏感性。这值得进一步研究，并可能有助于指导个体化治疗。
