Gene expression profile of peripheral blood mononuclear cells may contribute to the identification and immunological classification of breast cancer patients
Gene expression profile of peripheral blood mononuclear cells may contribute to the identification and immunological classification of breast cancer patients
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DOI：
10.1007/s12282-018-0920-2
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发表时间：
2019-05-01
期刊：
影响因子：
4
通讯作者：
Toi, Masakazu
中科院分区：
文献类型：
--
作者：
Suzuki, Eiji;Sugimoto, Masahiro;Toi, Masakazu
背景已有报道表明，在多种类型的癌症中，外周血单个核细胞(PBMC)的基因表达谱具有独特的基因表达特征。本研究旨在探讨乳腺癌患者外周血单核细胞的特异性基因表达谱，探讨免疫学对宿主抗肿瘤免疫应答的认识。方法采用RNA测序的方法，以健康志愿者为对照，对乳腺癌患者外周血单核细胞的基因表达进行综合分析。用MetaCore(Tm)进行路径富集化分析，寻找与癌症患者和人类外周血单个核细胞基因表达谱相关的分子通路。结果发现乳腺癌患者与健康志愿者相比具有显著的独特的基因表达特征，如Toll样受体(TLR)3和TLR4诱导的Toll/IL-1受体区适配分子1(TICAM1)特异性信号通路。独特的免疫基因表达谱也显示了将乳腺癌患者分为T细胞抑制组和单核细胞激活组等亚组的可能性，而不依赖于已知的乳腺癌表型。结论这些初步发现表明，评估PBMCs的基因表达模式可能是一种侵入性较小的诊断程序，也是揭示乳腺癌免疫学洞察的有用方法，包括用于癌症免疫治疗的生物标志物，如免疫检查点抑制疗法。
BackgroundIt has been reported that the gene expression profile of peripheral blood mononuclear cells (PBMCs) exhibits a unique gene expression signature in several types of cancer. In this study, we aimed to explore the breast cancer patient-specific gene expression profile of PBMCs and discuss immunological insight on host antitumor immune responses.MethodsWe comprehensively analyzed the gene expression of PBMCs by RNA sequencing in the breast cancer patients as compared to that of healthy volunteers (HVs). Pathway enrichment analysis was performed on MetaCore(tm) to search the molecular pathways associated with the gene expression profile of PBMCs in cancer patients compared with HVs.ResultsWe found a significant unique gene expression signature, such as the Toll-like receptor (TLR) 3- and TLR4-induced Toll/interleukin-1 receptor domain-containing adapter molecule 1 (TICAM1)-specific signaling pathway in the breast cancer patients as compared to that of healthy volunteers. Distinctive immunological gene expression profiles also showed the possibility of classifying breast cancer patients into subgroups such as T-cell inhibitory and monocyte-activating groups independent of known phenotypes of breast cancer.ConclusionsThese preliminary findings suggest that evaluation of gene expression patterns of PBMCs might be both a less invasive diagnostic procedure and a useful way to reveal immunological insight of breast cancer, including biomarkers for cancer immunotherapy, such as immune checkpoint inhibitor therapy.