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跨膜蛋白244(TMEM244)的高表达与T细胞淋巴瘤患者的总生存期较差相关。

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

作者信息

Chen Cunte, Chen Shaohua, Luo Gengxin, Wang Liang, Zeng Chengwu, Przybylski Grzegorz K, Li Yangqiu

机构信息

Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.

Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.

出版信息

Biomark Res. 2022 Jul 12;10(1):46. doi: 10.1186/s40364-022-00395-z.

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.

摘要

T细胞淋巴瘤(TCL)是一种侵袭性且基因异质性的恶性肿瘤,临床预后不良;因此,探索用于风险分层的生物标志物很有必要。先前的研究表明,跨膜蛋白244基因(TMEM244)在蕈样肉芽肿综合征(SS)中异位表达。在本研究中,通过分析两个大型数据集(GSE132550和GSE113113)的RNA测序数据,探索了TMEM244的表达水平及其对TCL患者的预后价值。这两个数据集包含来自基因表达综合数据库(GEO)的129例TCL患者和13名健康个体(HI),来自生物项目数据库的包含124例T细胞急性淋巴细胞白血病(T-ALL)患者的PRJCA002270数据集,以及24例TCL和29例T-ALL患者的外周血(PB)样本,还有来自我们临床中心(JNU)的11个正常CD3 + T细胞。结果表明,与JNU、GSE132550和GSE113113数据集中的正常CD3 + T细胞或T-ALL相比,TCL患者中TMEM244显著上调(P < 0.05)。然而,在JNU-T-ALL和PRJCA002270数据集中,T-ALL患者中未检测到TMEM244表达。受试者工作特征(ROC)曲线分析表明,与T-ALL相比,TMEM244表达在诊断TCL方面具有非常高的准确性(曲线下面积(AUC):99.4%;P < 0.001)。重要的是,高TMEM244表达与TCL患者的不良总生存期(OS)和较短的5年受限平均生存时间(RMST)显著相关,尤其是接受化疗的患者。总之,TMEM244除了在SS中表达外,在其他类型的TCL中也有表达,但在T-ALL中不表达。高TMEM244表达与TCL患者的不良OS相关,这可能是TCL患者预后分层的一种新型生物标志物,并有助于新型疗法的设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b97/9281042/95ff46c12d71/40364_2022_395_Fig1_HTML.jpg

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