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局灶性焦亡相关基因是三阴性乳腺癌脑转移的预后标志物。

Focal pyroptosis-related genes and are prognostic markers for triple-negative breast cancer with brain metastases.

作者信息

Huang Qian Fang, Fang Da Lang, Nong Bin Bin, Zeng Jian

机构信息

Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Department of Gynecology and Obstetrics, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

出版信息

Transl Cancer Res. 2021 Nov;10(11):4845-4858. doi: 10.21037/tcr-21-2182.

Abstract

BACKGROUND

Extensive research has shown the role of pyroptosis in the occurrence, progression, and prognosis of breast cancer. The study sought to screen important pyroptosis-related genes and their role in the prognosis of triple-negative breast cancer (TNBC) patients with brain metastasis (BM).

METHODS

The Gene Expression Omnibus database was used to obtain transcriptome data from primary TNBC and from TNBC BM patients. Differentially expressed genes (DEGs) between the primary tumors and BMs were analyzed, and the expression, prognostic significance, immune infiltration, function, and drug sensitivity of the pyroptosis genes in the DEGs were analyzed.

RESULTS

In both data sets, 456 genes differed between primary TNBC and TNBC BM. and were found to be important pyroptosis genes in DEGs, and significant differences in their expression in primary lesions and BMs were observed. Patients with a high expression of had a worse prognosis than low expression, while patients with a high expression of had a better prognosis than low expression. and were positively correlated with the infiltration of most immune cells; however, was negatively correlated with the infiltration of neural cell adhesion molecule 1 (CD56) bright natural killer cells and central memory cluster of differentiation 8 (CD8) T cells. Increased expression of is negatively correlated with high infiltration levels of central memory CD8 T cells and memory B cells.

CONCLUSIONS

Our findings suggest that and increase immune cell infiltration and may be potential targets for predicting and treating TNBC BM.

摘要

背景

大量研究表明细胞焦亡在乳腺癌的发生、发展和预后中发挥作用。本研究旨在筛选重要的细胞焦亡相关基因及其在三阴性乳腺癌(TNBC)脑转移(BM)患者预后中的作用。

方法

利用基因表达综合数据库获取原发性TNBC和TNBC BM患者的转录组数据。分析原发性肿瘤与BM之间的差异表达基因(DEG),并分析DEG中细胞焦亡基因的表达、预后意义、免疫浸润、功能和药物敏感性。

结果

在两个数据集中,原发性TNBC和TNBC BM之间有456个基因存在差异。发现 和 是DEG中的重要细胞焦亡基因,且观察到它们在原发性病变和BM中的表达存在显著差异。 高表达患者的预后比低表达患者差,而 高表达患者的预后比低表达患者好。 和 与大多数免疫细胞的浸润呈正相关;然而, 与神经细胞黏附分子1(CD56)明亮的自然杀伤细胞和分化簇8(CD8)中央记忆T细胞的浸润呈负相关。 的表达增加与中央记忆CD8 T细胞和记忆B细胞的高浸润水平呈负相关。

结论

我们的研究结果表明, 和 增加免疫细胞浸润,可能是预测和治疗TNBC BM的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4611/8797367/44c6bfcd1da9/tcr-10-11-4845-f1.jpg

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