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A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study.
Leukemia ( IF 9.944 ) Pub Date : 2020-02-20 , DOI: 10.1038/s41375-020-0757-5
Xiao-Peng Tian,Dan Xie,Wei-Juan Huang,Shu-Yun Ma,Liang Wang,Yan-Hui Liu,Xi Zhang,Hui-Qiang Huang,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,Xue-Yi Pan,Hai Lan,Guo-Wei Li,Lu Liu,Hui-Zheng Bao,Li-Yan Song,Tie-Bang Kang,Qing-Qing Cai

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.
更新日期:2020-02-21

 

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