toll样受体9 (TLR9)表达与细胞来源相关,并预测弥漫性大b细胞淋巴瘤的临床预后

IF 3.4 2区 医学 Q2 ONCOLOGY
Sulaf Abd Own, Ioanna Xagoraris, Konstantina Stathopoulou, Björn E Wahlin, Weicheng Ren, Mehran Ghaderi, Qiang Pan-Hammarström, Birgitta Sander, Karin E Smedby, Georgios Rassidakis
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引用次数: 0

摘要

背景:细胞起源(COO)分类之外的生物学见解可以支持弥漫性大b细胞淋巴瘤(DLBCL)的临床管理。我们研究toll样受体9 (TLR9)表达是否可以作为DLBCL的预后指标。方法:在4个公开的队列(n = 2474)中分析TLR9基因表达,并研究生发中心b细胞(GCB)和活化b细胞(ABC) DLBCL细胞系中TLR9蛋白表达。接下来,对120例经r - chop治疗的复发/难治性疾病(预后差,n = 50)或完全缓解(预后好,n = 70)患者的诊断样本进行TLR9蛋白表达分析。使用逻辑回归评估相关性,估计优势比(OR)和95%置信区间(CI)。结果:TLR9基因在ABC DLBCL中的表达高于外部队列中GCB DLBCL的表达,细胞系中蛋白的表达也得到了类似的结果。在患者样本中,TLR9蛋白高表达与非gcb型(p = 0.003)和预后不良(p = 0.0016)相关。在多变量分析中,在调整COO和其他临床特征后,高TLR9表达仍与不良预后相关(OR = 3.36, 95% CI 1.41-8.04)。探索性分析表明,ODN4084-F抑制TLR9活性后,ABC细胞系细胞生长下降。结论:TLR9与ABC/非gcb表型相关,是DLBCL不良预后的潜在预测因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Toll-like receptor 9 (TLR9) expression correlates with cell of origin and predicts clinical outcome in diffuse large B-cell lymphoma.

Background: Biological insights beyond the cell-of-origin (COO) classification can support clinical management in diffuse large B-cell lymphoma (DLBCL). We investigated if Toll-like receptor 9 (TLR9) expression could serve as a prognostic marker in DLBCL.

Method: TLR9 gene expression was analysed in four publicly available cohorts (n = 2474), and protein expression was investigated in germinal centre B-cell (GCB) and activated B-cell (ABC) DLBCL cell lines. Next, TLR9 protein expression was analysed in 120 diagnostic samples from R-CHOP-treated patients with relapsed/refractory disease (poor outcome, n = 50) or in complete remission (good outcome, n = 70). Associations were evaluated using logistic regression, estimating odds ratios (OR) and 95% confidence intervals (CI).

Results: TLR9 gene expression was higher in ABC DLBCL compared to GCB DLBCL in external cohorts, and similar results were obtained for protein expression in cell lines. In patient samples, high TLR9 protein expression correlated with non-GCB type (p = 0.003) and poor outcome (p = 0.0016). High TLR9 expression remained associated with poor outcome in multivariable analysis after adjusting for COO and other clinical features (OR = 3.36, 95% CI 1.41-8.04). In exploratory analyses, a decrease of cell growth in ABC cell lines following inhibition of TLR9 activity with ODN4084-F was suggested.

Conclusion: We conclude that TLR9 correlates with ABC/non-GCB phenotype and is a potential predictor of poor prognosis in DLBCL.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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