Meta-analysis of the clinical characteristics and prognostic relevance of NOTCH1 and FBXW7 mutation in T-cell acute lymphoblastic leukemia
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Rong-Bin Liu1,2,3,*, Jian-Gui Guo1,2,4,8,*, Tian-Ze Liu1,2,*, Cheng-Cheng Guo1,2,5, Xin-Xiang Fan6, Xiao Zhang1,2,3, Wei-Han Hu1,2,4 and Xiu-Yu Cai1,2,7
1State Key Laboratory of Oncology in South China, Guangzhou, China
2Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
3Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, China
4Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
5Department of Neurosurgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
6Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China
7Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, China
8Department of Radiation Oncology, The First People's Hospital of Foshan, Foshan, China
*These authors contributed equally to this work
Xiu-Yu Cai, email: [email protected]
Wei-Han Hu, email: [email protected]
Keywords: T-ALL, NOTCH1, FBXW7, prognosis, meta-analysis
Received: September 20, 2016 Accepted: April 26, 2017 Published: June 19, 2017
The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status. NOTCH1/FBXW7 mutations correlated significantly with better prognosis (5-year EFS: HR, 0.57; 95% confidence interval [CI], 0.46 to 0.68; P < 0.001 and 5-year OS: HR, 0.61; 95% CI, 0.51 to 0.74; P < 0.001). The HR for 5-year EFS and OS with NOTCH1 mutations were 0.63 (95% CI, 0.53 to 0.75) and 0.76 (95% CI, 0.60 to 0.95), respectively; with FBXW7 mutations, they were 0.82 (95% CI, 0.60 to 1.11) and 0.79 (95% CI, 0.55 to 1.12), respectively. However, differences between children and adults showed no significance. We conclude that the presence of NOTCH1/FBXW7 mutations is an independent prognostic factor for 5-year EFS and 5-year OS.
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