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Lymphoma

A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study

Abstract

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.

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Fig. 1: The study flowchart.
Fig. 2: Kaplan–Meier curves of progression-free survival, disease-free survival, and overall survival according to eleven-gene-based classifier in three cohorts.
Fig. 3: Nomogram A to predict progression-free survival of T-LBL patients.
Fig. 4: Selection of patients who benefit from BFM chemotherapeutic regimen with Nomogram.
Fig. 5: Nomogram B and Nomogram C to predict survival outcomes in three cohorts.

Data availability

The key raw data have been uploaded onto the Research Data Deposit public platform (RDD), with the approval RDD number of (RDDA2019000567). The microarray data have been deposited online under accession number (GSE138300).

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Acknowledgements

This work was supported by grants from National Key R&D Program of China (2017YFC1309001, 2016YFC1302305), National Natural Science Foundation of China (81603137, 81672686, 81973384), and Special Support Program of Sun Yat-sen University Cancer Center (PT19020401).

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Contributions

X-PT, DX, W-JH, S-YM contributed equally. Q-QC and X-PT designed the study. W-JH, S-YM, LW, Y-HL, XZ, H-QH, T-YL, H-LR, ML, FL, FZ, L-YZ, LL, X-LL, JL, BL, Z-HL, Q-LT, QL, C-KS, Q-LZ, R-FC, QS, KR, XG, X-NL, KY, Y-RS, X-DC, WD, WS, CS, HL, Z-GZ, JR, Q-NG, YZ, X-LM, YZ, C-LH, Y-RJ, YZ, H-YG, W-JH, Z-JX., X-YP, HL, G-WL, LL, H-ZB, L-YS, and T-BK obtained and assembled data. X-PT, W-JH, DX, and Q-QC analyzed and interpreted the data. X-PT and Q-QC wrote the manuscript. X-PT and W-JH did the statistical analysis. All authors reviewed the manuscript and approved the final version.

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Correspondence to Qing-Qing Cai.

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Tian, XP., Xie, D., Huang, WJ. et al. A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study. Leukemia 34, 2392–2404 (2020). https://doi.org/10.1038/s41375-020-0757-5

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