组织蛋白酶与头颈部恶性肿瘤发病风险的孟德尔随机化分析  

A Mendelian randomization study of the association between cathepsin expression levels and the risk of head and neck malignant tumor

作　　者：宋帆 孙鹏飞[2] 付正丰 SONG Fan;SUN Pengfei;FU Zhengfeng(The Second Clinical Medical School,Lanzhou University,Lanzhou 730030,China;Department of Radiotherapy,The Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二临床医学院,甘肃兰州730030 [2]兰州大学第二医院放疗科,甘肃兰州730030

出　　处：《兰州大学学报(医学版)》2025年第3期38-46,共9页Journal of Lanzhou University(Medical Sciences)

基　　金：甘肃省卫生健康行业科研计划资助项目(GSWSKY2023-04);兰州大学第二医院(第二临床医学院)“萃英科技创新”计划资助项目(CY2023-MS-A06)。

摘　　要：目的 基于全基因组关联研究数据进行孟德尔随机化(MR)分析,以评估9种组织蛋白酶与11类头颈部恶性肿瘤(眼恶性肿瘤、鼻咽癌、鼻腔及鼻窦恶性肿瘤、腮腺恶性肿瘤、唇恶性肿瘤、甲状腺恶性肿瘤及其独立亚型甲状腺乳头状癌和甲状腺滤泡腺癌、脑恶性肿瘤及其独立亚型胶质母细胞瘤和星形细胞瘤)之间的因果关联。方法 采用逆方差加权法作为效应评估的主分析方法,同时将MR-Egger回归、加权中位数法、基于众数的简单估计、基于众数的加权估计4种方法作为参考。运用Cochran's Q检验、MR-Egger截距法、MR-PRESSO法、留一法、漏斗图法评估结论的稳定性和可靠性。最后,进行反向MR分析以检验结论是否受到反向因果干扰。结果 正向MR逆方差加权法显示,组织蛋白酶F(CTSF)水平越高,鼻咽癌的风险越高(P=0.025),而组织蛋白酶S (CTSS)水平升高与脑恶性肿瘤的风险增加相关(P=0.031);组织蛋白酶O (CTSO)水平升高与甲状腺癌(P=0.028)及其独立亚型甲状腺滤泡腺癌(P=0.027)风险降低相关。未发现反向因果、异质性及水平多效性。结论 CTSF、CTSS和CTSO分别与鼻咽癌、脑恶性肿瘤、甲状腺癌及独立亚型甲状腺滤泡腺癌的发病风险存在潜在的因果关联。Objective Mendelian randomization(MR)analysis was performed with pooled data from genome-wide association studies to evaluate the causal relationship between 9 types of cathepsins and 11 types of head and neck malignant tumor(ocular malignancy,nasopharyngeal carcinoma,nasal and sinus malignancy,parotid gland malignancy,lip malignancy,thyroid malignancy,thyroid papilloma,thyroid follicular adenocarcinoma,brain malignancy,glioblastoma,astrocytoma).Methods The inverse variance weighting method was selected as the main method for effect evaluation,and the results of four methods,namely MR-Egger regression,weighted median method,simple estimation based on mode,and weighted estimation based on mode were used as references.The study's stability and reliability were assessed using Cochran's Q test,MR-Egger inter-cept method,MR-PRESSO method,leave-one-out analysis and funnel plot analysis.Finally,reverse MR was performed to test whether there was a reverse causality in the conclusion.Results MR inverse variance weighted method showed that higher levels of cathepsin F(CTSF)were associated with an increased risk of nasopharyngeal carcinoma(P=0.025).Elevated levels of cathepsin S(CTSS)were associated with an increased risk of brain malignancy(P=0.031).Elevated levels of cathepsin O(CTSO)were significantly associated with a reduced risk of thyroid cancer(P=0.028)and its subtypes of thyroid follicular adenocarcinoma(P=0.027).There was no reverse causality,heterogeneity or horizontal pleiotropy in this study.Conclusion CTSF,CTSS,and CTSO exhibit potential causal associations with the risk of developing nasopharyngeal carcino-ma,malignant brain tumors,thyroid cancer,and follicular thyroid carcinoma,respectively.

关 键 词：组织蛋白酶 头颈部恶性肿瘤 孟德尔随机化分析 全基因组关联研究 因果推断 

分 类 号：R739.91[医药卫生—肿瘤] R739.41[医药卫生—临床医学]