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

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.

Anticancer effects of disulfiram in T-cell malignancies through NPL4-mediated ubiquitin–proteasome pathway

“…It is known that the establishment of a prognosis prediction model and risk stratification at the molecular level for patients with hematologic malignancies plays an essential role in guiding treatment choices. [46][47][48] Therefore, a molecular-based prognosis model and risk stratification are needed to further improve prediction accuracy for patients with TCL and T-ALL. 8,49,50 The ANAPC1 protein in the ubiquitin-proteasome pathway is a cell cycle-regulating E3 ubiquitin ligase, which promotes cancer progression by controlling mitosis and the G1 phase of the cell cycle, and high ANAPC1 was associated with poor prognosis.…”

“…It is known that the establishment of a prognosis prediction model and risk stratification at the molecular level for patients with hematologic malignancies plays an essential role in guiding treatment choices 46–48 . Therefore, a molecular‐based prognosis model and risk stratification are needed to further improve prediction accuracy for patients with TCL and T‐ALL 8,49,50 .…”

TNFAIP3 mutation is an independent poor overall survival factor for patients with T‐cell acute lymphoblastic leukemia

“…PB samples were collected for deoxyribonucleic acid (DNA) extraction and PCR. The detailed PCR and Sanger sequencing parameters and PCR primers for TNFAIP3 were described in a previous publication 21,22,27 …”

“…The detailed PCR and Sanger sequencing parameters and PCR primers for TNFAIP3 were described in a previous publication. 21,22,27 Conclusion: TNFAIP3 mutation mainly occurs in adult T-ALL patients, and it was associated with adverse clinical outcomes for T-ALL patients; thus, it might be a biomarker for prognostic stratification.…”

High expression of TMEM244 is associated with poor overall survival of patients with T-cell lymphoma

“…T-cell lymphoma (TCL) originates from lymphoblastoid or mature T cells and accounts for 10–15% of non-Hodgkin lymphoma, which can be further subdivided into various subtypes [ 1 , 2 ]. TCL is a highly aggressive malignancy that exhibits hematologic and prognostic heterogeneity [ 3 ].…”