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一小部分肾细胞癌患者的 CD20+B 细胞浸润程度较高,与预后不良相关。

A minority-group of renal cell cancer patients with high infiltration of CD20+B-cells is associated with poor prognosis.

机构信息

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Department of Immunology, genetics and pathology, Uppsala University, Uppsala, Sweden.

出版信息

Br J Cancer. 2018 Oct;119(7):840-846. doi: 10.1038/s41416-018-0266-8. Epub 2018 Oct 8.

Abstract

BACKGROUND

The role of B-lymphocytes in solid tumours is unclear. Tumour biology studies have implied both anti- and pro-tumoural effects and prognostic studies have mainly linked B-cells to increased survival. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking.

METHODS

Following immunohistochemistry (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in an RCC discovery- and validation cohort. Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset.

RESULTS

IHC analyses of the discovery cohort identified a previously unrecognised subgroup of RCC patients with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed significantly shorter survival according to uni- and multi-variable analyses. The association between poor prognosis and high density of CD20+ B-cells was confirmed in the validation cohort. Analyses of the KIRC gene expression dataset using the B-cell signature confirmed findings from IHC analyses. Analyses of other gene expression datasets, representing 13 different tumour types, indicated that the poor survival-association of B-cells occurred selectively in RCC.

CONCLUSION

This exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.

摘要

背景

B 淋巴细胞在实体瘤中的作用尚不清楚。肿瘤生物学研究表明,B 淋巴细胞具有抗肿瘤和促肿瘤作用,预后研究主要表明 B 细胞与生存增加相关。本研究旨在分析肾细胞癌(RCC)中 B 淋巴细胞的临床相关性,因为缺乏关于其预后影响的信息。

方法

使用 CD20 抗体进行免疫组织化学(IHC)染色后,在 RCC 发现和验证队列中定量 CD20+ B 细胞的密度。还分析了 14 个公开的癌症基因表达数据集(包括肾透明细胞癌(KIRC)数据集)中 B 细胞浸润的表达或 B 细胞基因特征与生存的关联。

结果

发现队列的 IHC 分析确定了一组以前未被识别的 RCC 患者,其 CD20+ B 细胞浸润程度较高。根据单变量和多变量分析,B 细胞高浸润亚组的生存明显缩短。在验证队列中,也证实了 CD20+ B 细胞高密度与预后不良之间的关联。使用 B 细胞特征对 KIRC 基因表达数据集进行的分析证实了 IHC 分析的结果。对代表 13 种不同肿瘤类型的其他基因表达数据集的分析表明,B 细胞的不良预后关联仅选择性地发生在 RCC 中。

结论

这项探索性研究确定了一组以前未被识别的、具有高 CD20 定义的 B 细胞密度的 RCC 不良预后亚组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9691/6189087/9a025365f64e/41416_2018_266_Fig1_HTML.jpg

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