Differential SATB1 Expression Reveals Heterogeneity of Cutaneous T-Cell Lymphoma
Differential SATB1 Expression Reveals Heterogeneity of Cutaneous T-Cell Lymphoma
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SATB1 表达差异揭示皮肤 T 细胞淋巴瘤的异质性
DOI：
10.1016/j.jid.2020.05.120
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发表时间：
2021-02-19
影响因子：
6.5
通讯作者：
Wang, Yang
中科院分区：
文献类型：
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作者：
Gao, Yumei;Liu, Fengjie;Wang, Yang
SATB1 是皮肤 T 细胞淋巴瘤中重要的 T 细胞特异性染色质组织者，而其在蕈样肉芽肿 (MF) 中的表达和功能仍然不明确。我们的研究旨在调查 SATB1 在 170 名 MF 患者队列中的临床病理意义。 SATB1 的表达在各个临床阶段的 MF 患者中存在异质性。 SATB1 高表达与 MF 病例的表皮增生、嗜酸性粒细胞浸润、大细胞转化较少以及良好的预后相关。 SATB1 和 CD30 共表达可区分皮肤 CD30(+) 淋巴增殖性疾病和 MF 大细胞转化。 MF 系中 SATB1 沉默表明，SATB1 上调参与嗜酸性粒细胞募集的基因，包括信号转导子和转录激活子 3 和 IL13，并下调细胞周期进展中的基因，这可能解释了低 SATB1 表达病例的预后不良。此外，SATB1与PD-1表达呈负相关，表明SATB1阴性恶性T细胞处于耗尽状态。 SATB1 与 Toll 样受体表达呈正相关，表明高 SATB1 表达的 MF 病例中先天免疫激活。因此，可变的 SATB1 表达促进了 MF 患者病理学和临床结果的异质性。
SATB1 is an important T-cell specific chromatin organizer in cutaneous T-cell lymphoma, whereas its expression and function in mycosis fungoides (MF) remain ambiguous. Our study aimed to investigate the clinicopathological significance of SATB1 in a cohort of 170 patients with MF. SATB1 expression was heterogeneous among the patients with MF in each clinical stage. High SATB1 expression was associated with epidermal hyperplasia, eosinophil infiltration, less large-cell transformation, and favorable prognosis in MF cases. SATB1 and CD30 coexpression distinguished cutaneous CD30(+) lymphoproliferative disorders from MF large-cell transformation. SATB1 silencing in MF lines showed that SATB1 upregulated the genes involved in eosinophil recruitment, including signal transducer and activator of transcription 3 and IL13, and down regulated the genes in cell-cycle progression, which may explain the inferior prognosis for low SATB1-expressing cases. Moreover, SATB1 was inversely correlated with PD-1 expression, indicating an exhausted status of SATB1-negative malignant T cells. SATB1 was positively correlated with toll-like receptors expression, suggesting innate immune activation in high SATB1-expressing MF cases. Therefore, variable SATB1 expression promotes heterogeneity in pathology and clinical outcome of patients with MF.