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Leukemia. 2019 Apr 5. doi: 10.1038/s41375-019-0466-0. [Epub ahead of print]

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

Author information

1
State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
2
Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, China.
3
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
4
Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
5
Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
6
Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
7
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
8
Department of Pathology, The First People's Hospital of Foshan, Foshan, China.
9
Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
10
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
11
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
12
Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
13
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
14
Department of Oncology, Sun-Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
15
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
16
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
17
Department of Pathology, Hematological hospital of Chinese Academy of Medical Sciences, Tianjin, China.
18
Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
19
Department of Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, China.
20
Department of Hematology, Jiangxi Provincial Cancer Hospital, Nanchang, China.
21
Department of Pathology, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China.
22
Department of Hematology, Shunde Hospital of Southern Medical University, Shunde, China.
23
Department of Hematology, The First Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
24
Department of Pathology, The First Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
25
Department of Hematology and Oncology, Guangzhou First People's Hospital, Guangzhou, China.
26
Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
27
Department of Medical Oncology, Jiangmen Central Hospital, Jiangmen, China.
28
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
29
Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.
30
Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
31
Department of Hematology, The First People's Hospital of Dongguan, Dongguan, China.
32
Department of Oncology, Affiliated hospital of Guangdong Medical University, Guangzhou, China.
33
Department of Pathology, Guangdong Province Hospital for Women and Children Health Care, Guangzhou, China.
34
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
35
Department of Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China.
36
State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. xiedan@sysucc.org.cn.
37
State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. caiqq@sysucc.org.cn.
38
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. caiqq@sysucc.org.cn.

Abstract

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.

PMID:
30953029
DOI:
10.1038/s41375-019-0466-0

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