目的：分析干扰素基因刺激因子（STING）在肺腺癌中的表达及其与肺腺癌患者临床特征间的关系，探讨STING与内质网应激的相关性及其在调控肺腺癌进展中的作用机制。方法：利用TIMER 数据库分析STING 基因在泛癌水平的表达情况，利用UALCAN和HPA数据库分析STING 在肺腺癌组织中的表达及其与肺腺癌患者临床特征间的关系，利用Kaplan-Meier 生存函数分析STING 表达与肺腺癌患者OS 率间的关系。利用LinkedOmics 数据库对肺腺癌表达谱数据进行STING 基因共表达分析，对STING 相关差异表达基因（DEG）进行GO功能与KEGG 通路富集分析，通过GSEA 筛选STING 调控肺腺癌的潜在通路。使用STING激动剂diABZI 及内质网应激抑制剂TUDCA对肺腺癌A549 与H460 细胞进行处理，通过qPCR、WB法检测STING及内质网应激相关分子的表达，通过CCK-8法检测细胞增殖活力。结果：肺腺癌组织和细胞中STING的表达水平均显著低于正常肺组织（均P<0.01），STING 高表达肺腺癌患者5年OS率显著高于低表达患者（P<0.01），STING 的表达与肺腺癌患者的年龄、性别等临床特征密切相关（均P<0.01）。STING 高表达在肺腺癌外源性抗原处理及提呈等通路上存在富集（均P<0.01）。使用STING激动剂可显著诱导肺腺癌细胞发生内质网应激（P<0.05），STING诱导活化后肺腺癌细胞增殖活力显著下降（均P<0.01），内质网应激抑制剂能部分恢复STING活化诱导后下降的细胞活力（P<0.05）。结论：STING基因在肺腺癌中低表达，其表达下调与肺腺癌患者预后不良相关，其机制可能是STING通过诱导内质网应激而抑制肺腺癌细胞活力。

Objective: To analyze the expression of stimulator of interferon gene (STING) in lung adenocarcinoma and the correlation between clinical features of lung adenocarcinoma patients and the expression of STING, and to investigate the association of STING with endoplasmic reticulum (ER) stress, and the functions and mechanisms of STING in regulating the progression of lung adenocarcinoma. Methods: The expression of STING at pan-cancer level was analyzed by using TIMER database. The expression of STING in lung adenocarcinoma tissue and the correlation between STING expression and clinical features of lung adenocarcinoma patients were explored by using UALCAN and HPA database. The correlation between STING expression and overall survival (OS) rates of lung adenocarcinoma patients was analyzed by using Kaplan-Meier survival function. Analysis of the co-expressed genes with STING was performed based on the expression profile data of lung adenocarcinoma from LinkedOmics database. GO function and KEGG pathway analyses were conducted to investigate the differential expressed genes (DEGs) of STING, and GSEA was performed to explore the potential pathways through which STING might regulate lung adenocarcinoma. The STING agonist, diABZI, and the ER stress inhibitor, TUDCA, were used to treat lung adenocarcinoma cell lines, A549 and H460, and the expressions of STING and ER stress-associated molecules were examined by qPCR and Western blotting, and the cell vitality was detected by CCK-8 assays. Results: The expressions of STING in lung adenocarcinoma tissues and cells were significantly lower than those in normal lung tissues (all P<0.01). The 5-year OS rates of lung adenocarcinoma patients with high STING expression were notably higher than those of low-expression patients (P<0.01), and the expression of STING were closely correlated with clinical characteristics of the lung adenocarcinoma patients, such as age and gender (all P<0.01). High STING expression was enriched in pathways, such as exogenous antigen processing and presentation in lung adenocarcinoma (all P<0.01). The use of STING agonist significantly induced ER stress in lung adenocarcinoma (P<0.05). STING activation significantly lowered the vitality of lung adenocarcinoma cells (all P<0.01), which could be partly reversed by using the ER stress inhibitor (P<0.05). Conclusion: The expression of STING is downregulated in lung adenocarcinoma, which is closely associated with worse clinical prognosis of the lung adenocarcinoma patients. STING could inhibit lung adenocarcinoma cell vitality by inducing ER stress.

国家自然科学基金（No. 31970892）