Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Cells. 2021 Dec 10;10(12):3484. doi: 10.3390/cells10123484.
Many studies support a stepwise continuum of morphologic changes between atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma (ADC). Here we characterized gene expression patterns and the association of differentially expressed genes and immune tumor microenvironment behaviors in AAH to ADC during ADC development. Tumor tissues from nine patients with ADC and synchronous multiple ground glass nodules/lesions (GGN/Ls) were analyzed using RNA sequencing. Using clustering, we identified genes differentially and sequentially expressed in AAH and ADC compared to normal tissues. Functional enrichment analysis using gene ontology terms was performed, and the fraction of immune cell types was estimated. We identified up-regulated genes ( and ) with a stepwise change of expression from AAH to ADC and validated those expressions by quantitative PCR and immunohistochemistry. The immune cell profiles revealed increased B cell activities and decreased natural killer cell activities in AAH and ADC. A stepwise change of differential expression during ADC development revealed potential effects on immune function in synchronous precursors and in tumor lesions in patients with lung cancer.
许多研究支持非典型腺瘤样增生 (AAH) 和肺腺癌 (ADC) 之间形态学变化的逐步连续体。在这里，我们描述了在 ADC 发展过程中，AAH 向 ADC 转变过程中差异表达基因的基因表达模式及其与免疫肿瘤微环境行为的关联。使用 RNA 测序分析了 9 名 ADC 患者和同步多发磨玻璃结节/病变 (GGN/Ls) 的肿瘤组织。通过聚类，我们确定了与正常组织相比，在 AAH 和 ADC 中差异表达和顺序表达的基因。使用基因本体术语进行了功能富集分析，并估计了免疫细胞类型的分数。我们确定了上调基因 ( 和 )，它们在 AAH 到 ADC 的表达中呈逐步变化，并通过定量 PCR 和免疫组织化学验证了这些表达。免疫细胞图谱显示，AAH 和 ADC 中 B 细胞活性增加，自然杀伤细胞活性降低。ADC 发展过程中差异表达的逐步变化揭示了对肺癌患者同步前体和肿瘤病变中免疫功能的潜在影响。
