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近年来，国内外利用单细胞转录组测序技术对肺癌外周血单个核细胞(peripheral blood mononuclear cell, PBMC)的研究较少，其基因表达谱的动态变化规律及其在肺癌发生发展中的调控作用尚未完全阐明。本研究创新性地运用此技术，通过细胞聚类、亚群注释、特征基因筛选、加权基因共表达网络调控分析、生存分析等方法，系统解析3例晚期非小细胞肺癌患者(疾病组)与1例健康男性(对照组)PBMC的特征基因及基因表达调控网络的差异。研究显示，肺癌患者均表现出细胞角蛋白19片段水平升高；单细胞测序数据分析共鉴定出14个细胞亚群，涵盖9种主要细胞类型；在基因表达调控网络分析中，研究发现疾病组CD4~+T细胞中的特征基因乳酸脱氢酶B和淋巴毒素B处于基因共表达网络调控中心，白细胞介素-7处于网络调控外周，提示这3个基因在细胞功能和免疫反应中可能具有重要作用。乳酸脱氢酶B、淋巴毒素B和白细胞介素-7与肺癌分期及预后具有相关性(P<0.05)。综合分析显示，肺癌患者PBMC各细胞亚群在基因表达上具有异质性，特别是CD4~+T细胞中的特征基因乳酸脱氢酶B、白细胞介素-7、淋巴毒素B显示出作为潜在生物标志物的价值，有望成为肺癌诊断、预后评估的新型生物标志物和潜在治疗靶点。这些发现不仅为深入理解肺癌免疫调控机制提供了新的见解，也为筛选新型肺癌标志物以及开发治疗靶点提供了重要的理论依据，具有重大的临床转化意义。
Abstract：In recent years, there have been few studies on peripheral blood mononuclear cells(PBMC) in lung cancer using single-cell transcriptome sequencing technology, both domestically and internationally. The dynamic changes in gene expression profiles and their regulatory effects during the occurrence and progression of lung cancer have not been fully elucidated. Using cell clustering, subpopulation annotation, characteristic gene screening, weighted gene co-expression network analysis, survival analysis, and other methods, this study creatively used single-cell transcriptome sequencing technology to systematically examine differences in characteristic genes and gene expression regulatory networks of PBMC from three patients with advanced non-small cell lung cancer(disease group) and one healthy male(control group). The study revealed that all patients with lung cancer exhibited elevated levels of cytokeratin 19 fragments. Single-cell sequencing data identified a total of 14 cell subpopulations, encompassing nine major cell types. Gene expression regulatory network analysis showed that the characteristic genes lactate dehydrogenase B and lymphotoxin B in CD4~+T cells from the disease group occupied central positions in the gene co-expression network, while interleukin-7 was located at the periphery of the regulatory network. These results implied that these three genes might be crucial for immune response and cell function. Moreover, lactate dehydrogenase B, lymphotoxin B, and interleukin-7 were significantly correlated with lung cancer staging and prognosis(P<0.05). A comprehensive analysis revealed heterogeneity in gene expression among PBMC subsets in lung cancer patients, particularly high-lighting lactate dehydroge-nase B, interleukin-7, and lymphotoxin B in CD4~+T cells as potential biomarkers. These genes are expected to serve as novel biomar-kers and therapeutic targets for lung cancer diagnosis and prognosis. These findings not only provide new insights into the immune regulatory mechanisms of lung cancer but also offer a critical theoretical foundation for developing new lung cancer markers and therapeutic targets, with significant clinical translational potential.
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基本信息:
DOI：10.13417/j.gab.044.001171
中图分类号:R734.2
引用信息:
[1]田婷婷,侯嘉,马珊妮,等.3例晚期非小细胞肺癌患者单细胞测序分析[J].基因组学与应用生物学,2025,44(11):1171-1189.DOI:10.13417/j.gab.044.001171.
基金信息:
宁夏回族自治区重点研发计划项目(2023BEG02002); 宁夏自然科学基金项目(2024AAC03696)共同资助