TNFAIP3 mutation may be associated with favorable overall survival for patients with T-cell lymphoma

Cunte Chen; Zheng Chen; Ling Huang; Lingling Zhou; Lihua Zhu; Sichu Liu; Gengxin Luo; Wenyu Li; Chengwu Zeng; Yangqiu Li

doi:10.1186/s12935-021-02191-5

TNFAIP3 mutation may be associated with favorable overall survival for patients with T-cell lymphoma

Cancer Cell Int. 2021 Sep 15;21(1):490. doi: 10.1186/s12935-021-02191-5.

Authors

Cunte Chen^#¹, Zheng Chen^#¹, Ling Huang^#², Lingling Zhou³, Lihua Zhu⁴, Sichu Liu², Gengxin Luo⁵, Wenyu Li⁶, Chengwu Zeng⁷, Yangqiu Li⁸

Affiliations

¹ Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
² Department of Lymphoma, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.
³ Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁴ Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, China.
⁵ Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
⁶ Department of Lymphoma, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. liwenyu@gdph.org.cn.
⁷ Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. zengcw@jnu.edu.cn.
⁸ Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. tyangqiuli@jnu.edu.cn.

^# Contributed equally.

Abstract

Background: T-cell lymphoma (TCL) is highly aggressive and has a poor prognosis; thus, it is worth exploring biomarkers that may predict clinical outcomes and investigate their potential role in developing targeted therapies. In this study, we characterized the mutation pattern of tumor necrosis factor-alpha-inducing protein 3 (TNFAIP3) and its role in the prognosis of TCL patients.

Methods: Coding sequence (CDS) mutations in TNFAIP3 in TCL patients was explored using exome-sequencing data from 79 patients in our center (Guangdong Provincial People's Hospital, GDPH) and 544 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Additionally, non-CDS mutations in TNFAIP3 in 41 TCL patients from our center (JNU) were investigated by polymerase chain reaction (PCR) and Sanger sequencing. Furthermore, non-CDS mutations in TNFAIP3 in 47 TCL patients from Gene Expression Omnibus (GEO) dataset were explored.

Results: In the COSMIC database, TNFAIP3 mutations in TCL patients were located in the CDS, and the overall mutation frequency was 2.2%. However, TNFAIP3 mutations were not detected in the CDS of any of the samples in our center's datasets. Interestingly, non-CDS TNFAIP3 mutations were found in 14.6% and 4.3% of TCL patients in the JNU and GSE15842 dataset, respectively. Importantly, there was a clear trend showing that TCL patients with a TNFAIP3 mutation were associated with a longer 5-year restricted mean survival time (RMST) and favorable OS rate compared with those without a TNFAIP3 mutation in the JNU dataset [hazard ratio (HR) = 0.29, 95% confidence interval (CI) 0.07 to 1.31, P = 0.089]. Furthermore, TNFAIP3 mutations significantly correlated with T-cell large granular lymphocytic leukemia (T-LGLL) with a favorable prognosis in the JNU dataset (P = 0.002). Notably, the different mutation patterns of TNFAIP3 when comparing our center and the COSMIC datasets might be due to different ethnic and genetic backgrounds.

Conclusions: To the best of our knowledge, we for the first time describe that TNFAIP3 mutations in non-CDS regions are associated with favorable OS for TCL patients, which might be a potential biomarker for the prognostic stratification of Chinese TCL patients.

Keywords: Mutation pattern; Prognosis; T-cell lymphoma; TNFAIP3 mutation.

Abstract

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