Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma

• DOI: 10.1038/s41375-019-0466-0
• Publication Date: 2019-04-05T11:02:37Z
• Authors: Xiao-Peng Tian; Wei-Juan Huang; Hui-Qiang Huang; Yan-Hui Liu; Liang Wang; Xi Zhang; Tong-Yu Lin; Hui-Lan Rao; Mei Li; Fang Liu; Fen Zhang; Li-Ye Zhong; Li Liang; Xiao-Liang Lan; Juan Li; Bing Liao; Zhi-Hua Li; Qiong-Lan Tang; Qiong Liang; Chun-Kui Shao; Qiong-Li Zhai; Run-Fen Cheng; Qi Sun; Kun Ru; Xia Gu; Xi-Na Lin; Kun Yi; Yue-Rong Shuang; Xiao-Dong Chen; Wei Dong; Wei Sang; Cai Sun; Hui Liu; Zhi-Gang Zhu; Jun Rao; Qiao-Nan Guo; Ying Zhou; Xiang-Ling Meng; Yong Zhu; Chang-Lu Hu; Yi-Rong Jiang; Ying Zhang; Hong-Yi Gao; Wen-Jun He; Zhong-Jun Xia; Cheng-Lei Wu; Mei-Yin Zhang; Hui-Yun Wang; Dan Xie; Qing-Qing Cai
• Keywords: Male; 0301 basic medicine; T-Lymphocytes; Remission Induction; Hematopoietic Stem Cell Transplantation; Kaplan-Meier Estimate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Disease-Free Survival; 3. Good health; MicroRNAs; 03 medical and health sciences; Humans; Female; Proportional Hazards Models

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.