从一对双胞胎患者中鉴定结外 NK/T 细胞淋巴瘤的基因特征。

The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins.

机构信息

Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, PR China.

Department of Pathology and Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.

出版信息

BMC Cancer. 2021 Dec 6;21(1):1303. doi: 10.1186/s12885-021-09023-9.

DOI:10.1186/s12885-021-09023-9

PMID:34872521

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8650233/

Abstract

BACKGROUND

There is no unified treatment standard for patients with extranodal NK/T-cell lymphoma (ENKTL). Cancer neoantigens are the result of somatic mutations and cancer-specific. Increased number of somatic mutations are associated with anti-cancer effects. Screening out ENKTL-specific neoantigens on the surface of cancer cells relies on the understanding of ENKTL mutation patterns. Hence, it is imperative to identify ENKTL-specific genes for ENKTL diagnosis, the discovery of tumor-specific neoantigens and the development of novel therapeutic strategies. We investigated the gene signatures of ENKTL patients.

METHODS

We collected the peripheral blood of a pair of twins for sequencing to identify unique variant genes. One of the twins is diagnosed with ENKTL. Seventy samples were analyzed by Robust Multi-array Analysis (RMA). Two methods (elastic net and Support Vector Machine-Recursive Feature Elimination) were used to select unique genes. Next, we performed functional enrichment analysis and pathway enrichment analysis. Then, we conducted single-sample gene set enrichment analysis of immune infiltration and validated the expression of the screened markers with limma packages.

RESULTS

We screened out 126 unique variant genes. Among them, 11 unique genes were selected by the combination of elastic net and Support Vector Machine-Recursive Feature Elimination. Subsequently, GO and KEGG analysis indicated the biological function of identified unique genes. GSEA indicated five immunity-related pathways with high signature scores. In patients with ENKTL and the group with high signature scores, a proportion of functional immune cells are all of great infiltration. We finally found that CDC27, ZNF141, FCGR2C and NES were four significantly differential genes in ENKTL patients. ZNF141, FCGR2C and NES were upregulated in patients with ENKTL, while CDC27 was significantly downregulated.

CONCLUSION

We identified four ENKTL markers (ZNF141, FCGR2C, NES and CDC27) in patients with extranodal NK/T-cell lymphoma.

摘要

背景

结外 NK/T 细胞淋巴瘤（ENKTL）患者缺乏统一的治疗标准。癌症新生抗原是体细胞突变的结果，具有肿瘤特异性。体细胞突变数量的增加与抗癌作用相关。筛选癌细胞表面的 ENKTL 特异性新生抗原依赖于对 ENKTL 突变模式的理解。因此，确定 ENKTL 特异性基因对于 ENKTL 诊断、肿瘤特异性新生抗原的发现和新的治疗策略的发展至关重要。我们研究了 ENKTL 患者的基因特征。

方法

我们收集了一对双胞胎的外周血进行测序，以鉴定独特的变异基因。其中一个双胞胎被诊断为 ENKTL。对 70 个样本进行 Robust Multi-array Analysis（RMA）分析。采用弹性网络和支持向量机-递归特征消除两种方法筛选独特基因。然后，进行功能富集分析和通路富集分析。接着，进行免疫浸润的单样本基因集富集分析，并通过 limma 包验证筛选标志物的表达。

结果

我们筛选出 126 个独特的变异基因。其中，弹性网络和支持向量机-递归特征消除相结合筛选出 11 个独特基因。随后，GO 和 KEGG 分析表明了鉴定出的独特基因的生物学功能。GSEA 分析显示五个具有高特征评分的免疫相关通路。在 ENKTL 患者和具有高特征评分的组中，具有功能的免疫细胞比例均有大量浸润。我们最终发现，CDC27、ZNF141、FCGR2C 和 NES 是 ENKTL 患者中四个差异显著的基因。ZNF141、FCGR2C 和 NES 在 ENKTL 患者中上调，而 CDC27 则显著下调。