Jingwei Yu1, Jing Gao1, Zhihao Lu1, Jifang Gong1, Yanyan Li1, Bin Dong2, Zhongwu Li2, Xiaotian Zhang1, Lin Shen3. 1. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China. 2. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China. 3. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China. Electronic address: lin100@medmail.com.cn.
Abstract
AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AIM: 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). METHODS: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. RESULTS: 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 humangastric cancer cells was inversely correlated with the expression levels of MAP-tau and TUBB3, as in in vivo animal xenografts. CONCLUSIONS: 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.