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

Abstract

T-cell lymphoma (TCL) is an aggressive and genetically heterogeneous malignancy with adverse clinical outcomes; thus, it is worth exploring biomarkers for risk stratification. Previous studies have demonstrated that transmembrane protein 244 gene (TMEM244) is ectopically expressed in Sézary syndrome (SS). In this study, the expression level of TMEM244 and its prognostic value for TCL patients was explored by analyzing RNA-seq data of two large datasets (GSE132550 and GSE113113) containing 129 TCL patients and 13 healthy individuals (HIs) from the Gene Expression Omnibus (GEO) database, the PRJCA002270 dataset containing 124 patients with T-cell acute lymphoblastic leukemia (T-ALL) from the BioProject database, and peripheral blood (PB) samples of 24 TCL and 29 T-ALL patients, as well as 11 normal CD3 + T-cells from our clinical center (JNU). The results suggested that TMEM244 was significantly up-regulated in TCL patients compared with normal CD3 + T-cells or T-ALL in the JNU, GSE132550 and GSE113113 datasets (P < 0.05). However, TMEM244 shows no expression in patients with T-ALL in the JNU-T-ALL and PRJCA002270 datasets. The receiver operating characteristic (ROC) curve analysis indicated that TMEM244 expression had a very high accuracy in diagnosing TCL compared with T-ALL (area under the curve (AUC): 99.4%; P < 0.001). Importantly, high TMEM244 expression was significantly associated with poor OS and shorter 5-year restricted mean survival time (RMST) in TCL patients, especially those treated with chemotherapy. In summary, TMEM244 is also expressed in other types of TCL besides SS, but not in T-ALL. High TMEM244 expression is associated with poor OS in TCL patients, which might be a novel biomarker for prognostic stratification in TCL patients and facilitate the design of novel therapies.

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

“…The endpoint of this study was OS, and the OS was defined as the time from the date of diagnosis to the date of death or last follow‐up time. 8 , 16 , 22 , 23 , 24 , 25 Whole‐exome sequencing data from 121 T‐ALL patients in the PRJCA002270 dataset, including 96 children, 22 adults, and 3 cases of unknown age, were downloaded from the BioProject database ( https://ngdc.cncb.ac.cn/bioproject/browse/PRJCA002270 ). 26 …”

“… 9 , 10 , 11 , 12 Moreover, genetic alterations exert an important role in prognostic stratification in precision therapy. 13 , 14 , 15 , 16 , 17 Although multiple studies have been conducted to explore the role of genetic alterations combined with minimal residual disease (MRD) in risk stratification for T‐ALL, high heterogeneity has led to difficulty in accurately stratifying all patients. 14 , 18 Therefore, further exploration of novel biomarkers to improve risk stratification for T‐ALL patients is needed.…”

“…These genetic alterations lead to malignant transformation of T‐cells, resulting in high heterogeneity of T‐ALL cells 9–12 . Moreover, genetic alterations exert an important role in prognostic stratification in precision therapy 13–17 . Although multiple studies have been conducted to explore the role of genetic alterations combined with minimal residual disease (MRD) in risk stratification for T‐ALL, high heterogeneity has led to difficulty in accurately stratifying all patients 14,18 .…”

Novel Biomarkers in Cutaneous T Cell Lymphomas

“…Our study also revealed that higher expression of TMEM244 was observed either in CD4+ or in CD8+ subsets of memory cells (CD4RO+), which is in line with the immunophenotype of Sézary cells 49 . Furthermore, collaborating with us Chinese group showed that high expression of TMEM244 is associated with poor overall survival of patients with different forms of T-cell lymphoma, including CTCL 50 . Mechanistically, we showed that TMEM244 expression in SS cells is driven by specific hypomethylation of its promoter 48 .…”

TMEM244 Is a Long Non-Coding RNA Necessary for CTCL Cell Growth

“…Izykowska et al, were the first to pay attention to the TMEM244 gene, as it was identified among four other genes ( EHD1 , MTMR2 , RNF123 , and TOX ) to be involved in the rearrangements affecting gene expression in Sézary syndrome (SS) patients compared to controls [ 8 ]. Further studies showed that TMEM244 is expressed in T-cell lymphomas as a result of specific hypomethylation of its promoter, and this expression is associated with poor overall survival in T-cell lymphoma patients [ 9 , 10 ]. A significantly higher expression of TMEM244 was identified in Sézary syndrome patients, not only compared to healthy individuals but also to SS clinical mimickers, such as mycosis fungoides and erythrodermic manifestations of non-malignant diseases, therefore indicating its diagnostic potential.…”