College of Life Sciences, University of Chinese Academy of Sciences, Yuquan Road, Shijingshan District, Beijing 100049, China.
BGI Research, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
Hum Mol Genet. 2024 Feb 1;33(4):342-354. doi: 10.1093/hmg/ddad187.
Peripheral blood mononuclear cells (PBMCs) reflect systemic immune response during cancer progression. However, a comprehensive understanding of the composition and function of PBMCs in cancer patients is lacking, and the potential of these features to assist cancer diagnosis is also unclear. Here, the compositional and status differences between cancer patients and healthy donors in PBMCs were investigated by single-cell RNA sequencing (scRNA-seq), involving 262,025 PBMCs from 68 cancer samples and 14 healthy samples. We observed an enhanced activation and differentiation of most immune subsets in cancer patients, along with reduction of naïve T cells, expansion of macrophages, impairment of NK cells and myeloid cells, as well as tumor promotion and immunosuppression. Based on characteristics including differential cell type abundances and/or hub genes identified from weight gene co-expression network analysis (WGCNA) modules of each major cell type, we applied logistic regression to construct cancer diagnosis models. Furthermore, we found that the above models can distinguish cancer patients and healthy donors with high sensitivity. Our study provided new insights into using the features of PBMCs in non-invasive cancer diagnosis.
外周血单核细胞（PBMCs）反映了癌症进展过程中的全身免疫反应。然而，人们对外周血单核细胞在癌症患者中的组成和功能的全面理解仍存在不足，这些特征在癌症诊断中的潜在应用也尚不清楚。在这里，通过单细胞 RNA 测序（scRNA-seq）研究了 68 个癌症样本和 14 个健康样本中 262025 个 PBMCs，探讨了癌症患者与健康供体之间 PBMCs 的组成和状态差异。我们观察到癌症患者中大多数免疫亚群的激活和分化增强，同时幼稚 T 细胞减少，巨噬细胞扩增，NK 细胞和髓样细胞功能受损，以及肿瘤促进和免疫抑制。基于从每个主要细胞类型的加权基因共表达网络分析（WGCNA）模块中识别出的差异细胞类型丰度和/或枢纽基因等特征，我们应用逻辑回归构建了癌症诊断模型。此外，我们发现上述模型可以高灵敏度地区分癌症患者和健康供体。我们的研究为利用 PBMCs 的特征进行非侵入性癌症诊断提供了新的见解。
