GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL
GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL
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DOI：
10.1038/s41598-020-65463-6
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发表时间：
2020-05
影响因子：
4.6
通讯作者：
Y. Takashima;Momoko Hamano;J. Fukai;Y. Iwadate;K. Kajiwara;Tsutomu Kobayashi;Hiroaki Hondoh;R. Yamanak
中科院分区：
文献类型：
--
作者：
Y. Takashima;Momoko Hamano;J. Fukai;Y. Iwadate;K. Kajiwara;Tsutomu Kobayashi;Hiroaki Hondoh;R. Yamanak
原发性中枢神经系统淋巴瘤（PCNSL）是一种脑恶性非霍奇金B细胞淋巴瘤。标准的治疗方法是高剂量的甲氨蝶呤（MTX）为基础的化疗和推迟全脑放疗。然而，MTX耐药依赖性的整体表达和信号通路的变化及其与疾病的关系尚未阐明。在这里，我们在MTX耐药PCNSL细胞系（HKBML-MTX和TK-MTX）和PCNSL组织中使用下一代测序和基因集富集分析（GSEA）进行了全局表达分析。在等级评分中，HKBML-MTX和TK-MTX中列出的基因在PCNSL中富集，但表达差。在倍数变化中，部分PCNSL组织中差异表达的基因在HKBML-MTX和TK-MTX细胞中也被检测到; FOXD 2-AS 1和MMP 19在HKBML-MTX和TK-MTX中共同表达，FABP 5和CD 70在HKBML-MTX中特异性表达，CLCN 2、HOXB 9、INE 1和LRP 5L在TK-MTX中特异性表达，这可能为PCNSL MTX敏感性的预后标志物提供了组合。此外，PCNSL亚组，用分层聚类和Kaplan-Meier方法划分，包括20个在HKBML-MTX和TK-MTX中共同表达的基因，10个HKBML-MTX特异性表达的基因，和2个TK-MTX特异性表达的基因。这些结果表明，GSEA辅助的基因标签可以提供复发性PCNSL与MTX耐药的预后标志物的组合。
Primary central nervous system lymphoma (PCNSL) is a brain malignant non-Hodgkin’s B-cell lymphoma. The standard treatments are high-dose methotrexate (MTX)-based chemotherapies and deferred whole brain radiotherapy. However, MTX resistance-dependent global expression and signaling pathway changes and their relationship with prognoses have not yet been elucidated. Here, we conducted a global expression analysis with next-generation sequencing and gene set enrichment analysis (GSEA) in MTX-resistant PCNSL cell lines (HKBML-MTX and TK-MTX) and PCNSL tissues. In rank scores, genes listed in HKBML-MTX and TK-MTX were enriched in PCNSL with poor prognoses. In fold changes, a part of differentially-expressed genes in PCNSL tissues were also detected in HKBML-MTX and TK-MTX cells;FOXD2-AS1andMMP19were commonly expressed in both HKBML-MTX and TK-MTX,FABP5andCD70were HKBML-MTX-specifically expressed, andCLCN2,HOXB9,INE1, andLRP5Lwere TK-MTX-specifically expressed, which may provide a combination of prognostic markers on MTX-sensitivities in PCNSL. Additionally, PCNSL subgroups, divided with hierarchical clustering and Kaplan-Meier methods, included twenty commonly expressed genes in both HKBML-MTX and TK-MTX, ten HKBML-MTX-specifically expressed genes, and two TK-MTX-specifically expressed genes. These results suggest that the GSEA-assisted gene signatures can provide a combination for prognostic markers in recurrent PCNSL with MTX resistances.