【摘要】 目的 基于生物信息学分析甲状腺乳头状癌中CD8~+T细胞亚型及其分化相关的免疫景观与基因表达模式，构建预后模型并进行免疫浸润特征分析。方法 整合单细胞RNA测序数据与Bulk转录组测序数据，通过差异表达分析、细胞分化轨迹分析、一致性聚类、LASSO-Cox比例风险回归等方法，筛选CD8+T细胞亚型相关预后基因，构建并评估风险评分预后模型，并基于该模型进行免疫浸润分析和免疫治疗反应预测。结果 本研究将甲状腺乳头状癌肿瘤微环境中的CD8+T细胞分为6种亚型，并筛选出LAIR2、RGS2、DEDD2、HSPA6、KLRB1、DNAJB1、CCL5、CX3CR1、MT1M这9个预后基因构建预后模型。训练集、验证集和总集的受试者操作特征曲线显示出预后模型对甲状腺乳头状癌患者3、5、10年总生存期具有良好的预测效能。高风险组患者的总生存期短于低风险组（P=0.021），且免疫细胞浸润程度更低，低风险组对免疫治疗的应答率更高（P=0.04）。结论 该预后模型可有效预测甲状腺乳头状癌患者的预后、免疫浸润特征和免疫治疗反应，为临床预后评估及制定个性化治疗方案提供了理论依据。更多还原

【Abstract】 Objective To analyze the immune landscape and gene expression patterns associated with CD8+T-cell subtypes in papillary thyroid carcinoma by using bioinformatics, construct a prognostic model, and performe analyses of immune infiltration characteristics. Methods We integrated single-cell RNA sequencing and Bulk transcriptomic data,using differential expression analysis, cell differentiation trajectory analysis, consensus clustering, and LASSO-Cox proportional hazards regression to identify CD8+T-cell subtype-associated prognostic genes. Then we developed and evaluated a risk-score prognostic model and used it to analyze immune infiltration and predict responses to immunotherapy.Results We classified tumor-infiltrating CD8~+T-cells in papillary thyroid carcinoma into six subtypes, identified nine prognostic genes(LAIR2, RGS2, DEDD2, HSPA6, KLRB1, DNAJB1, CCL5, CX3 CR1, and MT1M), and constructed a prognostic model. Receiver operating characteristic(ROC) curves for the training, validation, and combined cohorts demonstrated that the model had good predictive performance for 3-, 5-, and 10-year overall survival in patients with papillary thyroid carcinoma. Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group(P=0.021) and exhibited lower levels of immune cell infiltration, while the low-risk group showed a higher response rate to immunotherapy(P=0.04). Conclusion This prognostic model can effectively predict the prognosis,immune infiltration characteristics, and response to immunotherapy in patients with papillary thyroid carcinoma,providing a theoretical basis for clinical prognostic assessment and the development of personalized treatment strategies.更多还原