从自身免疫性炎症到恶性瘤:RA-状细胞肺癌轴的因果遗传证据
Jianbin Li1,2, Suiran Li1,2, Yuxiu Ka1,2
1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
Arthritis research & therapy
|December 2, 2025
概括
风湿性关节炎 (RA) 特别增加了状细胞肺癌的风险,而不是其他亚型. 多变量门德尔随机化澄清了这种因果关系,解释了吸烟. 建议针对RA患者进行有针对性的查.
科学领域:
- 类风湿病学 类风湿病学
- 在瘤学瘤学.
- 遗传流行病学遗传流行病学
背景情况:
- 类风湿性关节炎 (RA) 与肺癌之间的联系受到争论,不一致的发现通常是由于吸烟和缺乏亚型分析.
- 之前的研究还没有充分解决与RA相关的特定组织学肺癌亚型.
研究的目的:
- 为了澄清类风湿性关节炎和肺癌风险之间的关联,考虑特定的组织学亚型.
- 通过临床,机器学习和遗传方法的三角化研究RA和肺癌之间的因果关系.
主要方法:
- 中国队列 (8,867名受试者) 的倾向性比分匹配,以评估RA与肺癌亚型 (腺癌,状细胞癌,小细胞癌) 的关联.
- 基于22个临床特征,开发机器学习模型 (逻辑回归,随机森林,XGBoost) 来预测肺癌风险.
- 多变量孟德尔随机化 (MVMR) 分析使用来自欧洲人口的大规模GWAS数据来确定RA对状细胞肺癌的因果作用,以吸烟为准.
主要成果:
- RA显著增加平细胞肺癌的风险 (OR=2.415),但不是腺癌或小细胞癌.
- 机器学习模型显示肺癌的预测能力有限 (AUC=0.57-0.68).
- 在调整吸烟后的MVMR分析揭示了RA在促进状细胞肺癌 (OR=1.02) 的因果作用.
结论:
- 风湿性关节炎与状细胞肺癌的风险增加特别相关.
- 多变量门德尔随机化成功确定了因果关系,解决了吸烟引起的混.
- 研究结果表明,针对RA患者进行向状细胞肺癌查,需要进行跨人群验证.
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