嗜酸性粒细胞计数在介导哮喘与结肠癌关联中的作用。
Role of eosinophil counts in mediating the association between asthma and colon cancer.
作者信息
Zhan Zhi-Qing, Huang Ze-Min, Xie Zhi-Xin, Zhou Hao-Bin, Luo Yu-Hua, Chen Pei-Zhen, Luo Tian-Ye, Sun Baoqing, Cheng Zhangkai J
机构信息
Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Clin Transl Allergy. 2024 Dec;14(12):e70012. doi: 10.1002/clt2.70012.
BACKGROUND
Epidemiological findings regarding the association between asthma and the risk of colon cancer (CC) are inconsistent. The causality and potential molecular mechanisms underlying asthma, eosinophil count, and CC remain unknown.
METHODS
We performed Mendelian randomization (MR) analysis to investigate the causality between asthma and CC and attempted to demonstrate that asthma indirectly affects CC mediated by eosinophil count through mediation analysis. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Multiple bioinformatics tools were applied to further investigate the underlying mechanisms related to eosinophils that contribute to the pathogenesis of both asthma and CC.
RESULTS
MR with mediation analyses suggested that eosinophil count may play a role in the mechanism through which asthma reduces the risk of CC. Our bioinformatic analyses identified PPP1R14A as a potential therapeutic target and an eosinophil-associated biomarker for CC patients. Higher expression of PPP1R14A may be associated with a poorer prognosis in CC patients. Additionally, the lysosome pathway emerges as a shared eosinophil-related pathway in both asthma and CC.
CONCLUSIONS
Eosinophils may contribute to a lower risk of CC in patients with asthma. PPP1R14A is a potential therapeutic target and biomarker for CC.
背景
关于哮喘与结肠癌（CC）风险之间关联的流行病学研究结果并不一致。哮喘、嗜酸性粒细胞计数与CC之间潜在的因果关系及分子机制仍不清楚。
方法
我们进行了孟德尔随机化（MR）分析，以研究哮喘与CC之间的因果关系，并试图通过中介分析证明哮喘通过嗜酸性粒细胞计数间接影响CC。进行了敏感性分析和多变量MR以检验我们研究结果的稳健性。应用多种生物信息学工具进一步研究与嗜酸性粒细胞相关的潜在机制，这些机制导致了哮喘和CC的发病。
结果
带有中介分析的MR表明，嗜酸性粒细胞计数可能在哮喘降低CC风险的机制中起作用。我们的生物信息学分析确定PPP1R14A为CC患者的潜在治疗靶点和嗜酸性粒细胞相关生物标志物。PPP1R14A的高表达可能与CC患者较差的预后相关。此外，溶酶体途径是哮喘和CC中共同的嗜酸性粒细胞相关途径。
结论
嗜酸性粒细胞可能导致哮喘患者患CC的风险较低。PPP1R14A是CC的潜在治疗靶点和生物标志物。
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