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乳腺癌蛋白质谱分析揭示免疫抑制因子的表达及与患者预后相关的特征

英文原题:Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome.

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Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome.

PubMed 2022/09/19(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

在癌症中,肿瘤细胞与肿瘤微环境之间复杂的相互作用导致信号传导过程的调节。通过评估癌症组织中大量蛋白质和蛋白质变体的表达,可以获得关于信号通路激活和免疫景观状态的广泛信息,并可能提供关于治疗反应的有价值信息。通过高通量Western blotting分析了来自84名患者(无辅助治疗)队列的存档乳腺癌组织,并检查了涵盖核心癌症通路和免疫细胞标志物的150种蛋白质的表达。通过评估CD8α、CD11c、CD16和CD68的表达,确定了免疫细胞浸润,并揭示了无事件患者生存与免疫细胞浸润之间的强相关性。TIL(肿瘤浸润淋巴细胞)的存在与Jak/Stat信号通路和凋亡过程的显著激活相关。非免疫浸润肿瘤中PPARγ(pS112)磷酸化升高提示了一种以PPARγ磷酸化增加为特征的乳腺癌新型免疫逃逸机制。多重免疫细胞标志物评估和肿瘤组织的蛋白质谱分析提供了功能性信号数据,有助于乳腺癌患者分层。

展开英文摘要原文

In cancer, the complex interplay between tumor cells and the tumor microenvironment results in the modulation of signaling processes. By assessing the expression of a multitude of proteins and protein variants in cancer tissue, wide-ranging information on signaling pathway activation and the status of the immunological landscape is obtainable and may provide viable information on the treatment response. Archived breast cancer tissues from a cohort of 84 patients (no adjuvant therapy) were analyzed by high-throughput Western blotting, and the expression of 150 proteins covering central cancer pathways and immune cell markers was examined.

By assessing CD8α, CD11c, CD16 and CD68 expression, immune cell infiltration was determined and revealed a strong correlation between event-free patient survival and the infiltration of immune cells. The presence of tumor-infiltrating lymphocytes was linked to the pronounced activation of the Jak/Stat signaling pathway and apoptotic processes.

The elevated phosphorylation of PPARγ (pS112) in non-immune-infiltrated tumors suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ phosphorylation. Multiplexed immune cell marker assessment and the protein profiling of tumor tissue provide functional signaling data facilitating breast cancer patient stratification.

论文信息

作者
Ruoff F、Kersten N、Anderle N、Jerbi S、Stahl A、Koch A、Staebler A、Hartkopf A
单位
NMI Natural and Medical Sciences Institute at the University of Tuebingen, 72770 Reutlingen, Germany.Germany
期刊
Cancers2022 Sep 19
原文标识
PubMed 36139700 · DOI 10.3390/cancers14184542