DataSheet_1_Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution.docx

BackgroundLung cancer is the deadliest and most diagnosed type of cancer worldwide. The 5-year survival rate of lung adenocarcinoma (LUAD) dropped significantly when tumor stages advanced. Patients who received surgically resecting at the pre-invasive stage had a 5-year survival rate of nearly 100%. However, the study on the differences in gene expression profiles and immune microenvironment among pre-invasive LUAD patients is still lacking.MethodsIn this study, the gene expression profiles of three pre-invasive LUAD stages were compared using the RNA-sequencing data of 10 adenocarcinoma in situ (AIS) samples, 12 minimally invasive adenocarcinoma (MIA) samples, and 10 invasive adenocarcinoma (IAC) samples.ResultsThe high expression levels of PTGFRN (Hazard Ratio [HR] = 1.45; 95% Confidence Interval [CI]: 1.08-1.94; log-rank P = 0.013) and SPP1 (HR = 1.44; 95% CI: 1.07-1.93; log-rank P = 0.015) were identified to be associated with LUAD prognosis. Moreover, the early LUAD invasion was accompanied by the enhancement of antigen presentation ability, reflected by the increase of myeloid dendritic cells infiltration rate (Cuzick test P < 0.01) and the upregulation of seven important genes participating in the antigen presentation, including HLA-A (Cuzick test P = 0.03), MICA (Cuzick test P = 0.01), MICB (Cuzick test P = 0.01), HLA-DPA1 (Cuzick test P = 0.04), HLA-DQA2 (Cuzick test P < 0.01), HLA-DQB1 (Cuzick test P = 0.03), and HLA-DQB2 (Cuzick test P < 0.01). However, the tumor-killing ability of the immune system was inhibited during this process, as there were no rising cytotoxic T cell activity (Cuzick test P = 0.20) and no increasing expression in genes encoding cytotoxic proteins. ConclusionIn all, our research elucidated the changes in the immune microenvironment during early-stage LUAD evolution and may provide a theoretical basis for developing novel early-stage lung cancer therapeutic targets.

背景：肺癌是全球范围内最为致命且诊断率最高的癌症类型。当肺腺癌（LUAD）的肿瘤分期进展时，其五年生存率显著下降。在原位癌（AIS）阶段接受手术切除的患者，其五年生存率接近100%。然而，关于侵袭前期LUAD患者基因表达谱和免疫微环境差异的研究尚显不足。方法：本研究通过对比10例原位癌（AIS）样本、12例微创腺癌（MIA）样本和10例侵袭性腺癌（IAC）样本的RNA测序数据，对三个侵袭前期LUAD阶段的基因表达谱进行了比较。结果：PTGFRN（风险比 [HR] = 1.45；95% 置信区间 [CI]：1.08-1.94；log-rank P = 0.013）和SPP1（HR = 1.44；95% CI：1.07-1.93；log-rank P = 0.015）的高表达水平被识别为与LUAD预后相关。此外，早期LUAD侵袭伴随着抗原呈递能力的增强，这一现象体现在髓样树突状细胞浸润率的增加（Cuzick测试P < 0.01）以及七个参与抗原呈递的重要基因的上调，包括HLA-A（Cuzick测试P = 0.03）、MICA（Cuzick测试P = 0.01）、MICB（Cuzick测试P = 0.01）、HLA-DPA1（Cuzick测试P = 0.04）、HLA-DQA2（Cuzick测试P < 0.01）、HLA-DQB1（Cuzick测试P = 0.03）和HLA-DQB2（Cuzick测试P < 0.01）。然而，在此过程中，免疫系统杀伤肿瘤的能力受到抑制，因为并未观察到细胞毒性T细胞活性的上升（Cuzick测试P = 0.20）以及编码细胞毒性蛋白的基因表达增加。结论：总之，本研究阐明了侵袭前期LUAD演变过程中免疫微环境的变化，并可能为开发新型早期肺癌治疗靶点提供理论依据。