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三阴性乳腺癌免疫相关预后生物标志物的研究进展。

Development of an immune-related prognostic biomarker for triple-negative breast cancer.

机构信息

Department of Pathology, The First Affiliated Hospital of Guangdong University of Pharmacy, Guangzhou, China.

Department of Pathology, Maternity & Child Healthcare Hospital of Longhua District, Shenzhen, China.

出版信息

Ann Med. 2022 Dec;54(1):1212-1220. doi: 10.1080/07853890.2022.2067894.

DOI:10.1080/07853890.2022.2067894
PMID:35481432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9068007/
Abstract

Oncology studies employing digital dissection methodologies have provided some insight on the biological features of tumor microenvironment of Triple-negative breast cancer (TNBC), but molecular diagnostics rarely have therapeutic impact. We aimed to identify a novel prognostic biomarker to investigate immune characteristics of TNBC using transcriptomic features. We extracted whole transcriptome from breast cancer tissue of 30 TNBC patients and then used bioinformatics approaches to characterize the different immune cell contents in tumor tissue and para-cancerous tissue. We extract 2 indicators to describe the major differences in immune infiltration in the microenvironment between tumor tissue and para-cancerous tissue. We then combined the 2 indicators that represent the levels of increased and decreased infiltration in each sample to obtain the Immune Infiltration Score (IIS). Then we compared the tumor-infiltrating immune cell contents and immune infiltrating status in TNBC samples with CIBERSORT and ESTIMATE score to validate the IIS. Finally, 132 TNBC patients from the Cancer Genome Atlas program (TCGA) dataset was used to validate the predictive power of IIS. 4 types of upregulated and 4 types of downregulated immune cells were identified in the tumor tissue samples of the TNBC patients. Then we developed a novel biomarker, IIS. Results showed that IIS score can clearly separate cancer and para-cancerous tissue. Using the same cutoff value of 0 in the TNBC-TCGA cohort, we show that those patients with a higher IIS had significantly higher PD-L1 expression and shorter progression-free survival time than those with a lower IIS value, indicating IIS score can be generalized to other TNBC datasets. we explored the immune infiltration landscape in 30 TNBC patients and provided IIS as a novel and reliable biomarker to evaluate the progression-free survival and prognosis of the TNBC patients.

摘要

肿瘤学研究采用数字解剖方法对三阴性乳腺癌 (TNBC) 的肿瘤微环境生物学特征提供了一些见解,但分子诊断很少有治疗效果。我们旨在通过转录组特征来鉴定一种新的预后生物标志物,以研究 TNBC 的免疫特征。我们从 30 名 TNBC 患者的乳腺癌组织中提取全转录组,然后使用生物信息学方法来描述肿瘤组织和癌旁组织中不同免疫细胞的含量。我们提取了 2 个指标来描述肿瘤组织和癌旁组织之间微环境中免疫浸润的主要差异。然后,我们将代表每个样本中浸润程度增加和减少的 2 个指标相结合,以获得免疫浸润评分 (IIS)。然后,我们使用 CIBERSORT 和 ESTIMATE 评分比较了 TNBC 样本中的肿瘤浸润免疫细胞含量和免疫浸润状态,以验证 IIS。最后,使用癌症基因组图谱计划 (TCGA) 数据集的 132 名 TNBC 患者来验证 IIS 的预测能力。在 TNBC 患者的肿瘤组织样本中鉴定出 4 种上调和 4 种下调的免疫细胞。然后我们开发了一种新的生物标志物,IIS。结果表明,IIS 评分可以清楚地区分癌症和癌旁组织。在 TNBC-TCGA 队列中,使用相同的 0 截止值,我们发现那些具有较高 IIS 的患者的 PD-L1 表达明显更高,无进展生存期更短,而那些具有较低 IIS 值的患者则更短,这表明 IIS 评分可以推广到其他 TNBC 数据集。我们探索了 30 名 TNBC 患者的免疫浸润情况,并提供了 IIS 作为一种新的可靠生物标志物,用于评估 TNBC 患者的无进展生存期和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/4e0e5f8733b7/IANN_A_2067894_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/52aa8e6ead02/IANN_A_2067894_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/4e2485710ec1/IANN_A_2067894_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/4e0e5f8733b7/IANN_A_2067894_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/52aa8e6ead02/IANN_A_2067894_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/4e2485710ec1/IANN_A_2067894_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/9068007/4e0e5f8733b7/IANN_A_2067894_F0003_C.jpg

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本文引用的文献

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NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer.NPM1 上调 PD-L1 的转录并抑制三阴性乳腺癌中的 T 细胞活性。
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