直肠癌炎症蛋白因子的遗传驱动:孟德尔随机化方法在临床预后研究中的应用
目的 利用孟德尔随机化(MR)方法,探索炎症蛋白因子与直肠癌风险之间的因果关系,为直肠癌的预防和治疗提供新的策略.方法 从全基因组关联分析(GWAS)数据集中选取与直肠癌相关的信息,使用91个炎症蛋白因子作为暴露变量.采用双样本MR分析模型评估炎症蛋白因子与直肠癌的因果联系,并通过异质性、多效性和敏感性分析评估结果的稳健性.使用5种MR分析模型,包括逆方差加权法(IVW)、加权中位数法(Weighted median)、模型选择法(MR-Egger)、简单模型法和加权模型法.选择2021年12月～2023年12月南方医科大学南方医院收治的86 例未经治疗的直肠腺癌患者开展临床研究,使用RT-q...
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| Published in | 南方医科大学学报 Vol. 44; no. 7; pp. 1361 - 1369 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
南方医科大学南方医院普通外科,广东 广州 511340
2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1673-4254 |
| DOI | 10.12122/j.issn.1673-4254.2024.07.16 |
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| Abstract | 目的 利用孟德尔随机化(MR)方法,探索炎症蛋白因子与直肠癌风险之间的因果关系,为直肠癌的预防和治疗提供新的策略.方法 从全基因组关联分析(GWAS)数据集中选取与直肠癌相关的信息,使用91个炎症蛋白因子作为暴露变量.采用双样本MR分析模型评估炎症蛋白因子与直肠癌的因果联系,并通过异质性、多效性和敏感性分析评估结果的稳健性.使用5种MR分析模型,包括逆方差加权法(IVW)、加权中位数法(Weighted median)、模型选择法(MR-Egger)、简单模型法和加权模型法.选择2021年12月～2023年12月南方医科大学南方医院收治的86 例未经治疗的直肠腺癌患者开展临床研究,使用RT-qPCR技术定量分析程序性死亡配体1(PD-L1)、轴突诱导蛋白1(AXIN1)和β-神经生长因子(β-NGF)基因表达,使用Spearman秩相关系数分析基因表达与临床特征(包括吸烟情况、肿瘤最大直径、是否有转移、肿瘤-淋巴结-转移分期、分化程度和病理分型)之间的相关性.结果 MR分析显示AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040;IVW模型)、β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;IVW模型)(OR=0.884,95%CI:0.784-0.998,P=0.047,Weighted median模型)和PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028,IVW模型)风险降低有与直肠癌显著的因果关系.研究中不存在异质性(IVW法和MR Egger法检测的P>0.05),不存在多效性(P>0.05),模型稳定.敏感性分析显示,AXIN1、β-NGF和PD-L1的剩余单核苷酸多态性(SNP)效应值的均值分别为-0.1425、-0.0973和-0.1011,均与各自的主效应值-0.144、-0.1和-0.1接近,验证了结果的可靠性.临床研究显示,PD-L1基因的表达量与直肠癌的TNM分期显著相关,尤其是在TNM分期IV期患者中,PD-L1的表达量显著高于I、II、III期(P=0.007).AXIN1和β-NGF基因的表达量与肿瘤的分化程度显著相关;低分化的直肠癌样本中,AXIN1和β-NGF的表达量显著高于中分化和高分化样本(P<0.001).结论 炎症蛋白因子AXIN1、β-NGF和PD-L1的水平降低与直肠癌风险降低 |
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| AbstractList | 目的 利用孟德尔随机化(MR)方法,探索炎症蛋白因子与直肠癌风险之间的因果关系,为直肠癌的预防和治疗提供新的策略.方法 从全基因组关联分析(GWAS)数据集中选取与直肠癌相关的信息,使用91个炎症蛋白因子作为暴露变量.采用双样本MR分析模型评估炎症蛋白因子与直肠癌的因果联系,并通过异质性、多效性和敏感性分析评估结果的稳健性.使用5种MR分析模型,包括逆方差加权法(IVW)、加权中位数法(Weighted median)、模型选择法(MR-Egger)、简单模型法和加权模型法.选择2021年12月～2023年12月南方医科大学南方医院收治的86 例未经治疗的直肠腺癌患者开展临床研究,使用RT-qPCR技术定量分析程序性死亡配体1(PD-L1)、轴突诱导蛋白1(AXIN1)和β-神经生长因子(β-NGF)基因表达,使用Spearman秩相关系数分析基因表达与临床特征(包括吸烟情况、肿瘤最大直径、是否有转移、肿瘤-淋巴结-转移分期、分化程度和病理分型)之间的相关性.结果 MR分析显示AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040;IVW模型)、β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;IVW模型)(OR=0.884,95%CI:0.784-0.998,P=0.047,Weighted median模型)和PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028,IVW模型)风险降低有与直肠癌显著的因果关系.研究中不存在异质性(IVW法和MR Egger法检测的P>0.05),不存在多效性(P>0.05),模型稳定.敏感性分析显示,AXIN1、β-NGF和PD-L1的剩余单核苷酸多态性(SNP)效应值的均值分别为-0.1425、-0.0973和-0.1011,均与各自的主效应值-0.144、-0.1和-0.1接近,验证了结果的可靠性.临床研究显示,PD-L1基因的表达量与直肠癌的TNM分期显著相关,尤其是在TNM分期IV期患者中,PD-L1的表达量显著高于I、II、III期(P=0.007).AXIN1和β-NGF基因的表达量与肿瘤的分化程度显著相关;低分化的直肠癌样本中,AXIN1和β-NGF的表达量显著高于中分化和高分化样本(P<0.001).结论 炎症蛋白因子AXIN1、β-NGF和PD-L1的水平降低与直肠癌风险降低 |
| Abstract_FL | Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention. |
| Author | 张学华 李高桦 王亚楠 李和平 |
| AuthorAffiliation | 南方医科大学南方医院普通外科,广东 广州 511340 |
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| Author_FL | LI Gaohua ZHANG Xuehua LI Heping WANG Yanan |
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| DocumentTitle_FL | Genetic drivers for inflammatory protein markers in colorectal cancer:a Mendelian randomization approach to clinical prognosis study |
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| Keywords | clinical study colorectal cancer 临床研究 孟德尔随机化 inflammatory protein markers Mendelian randomization 直肠癌 炎症蛋白因子 |
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| Snippet | 目的 利用孟德尔随机化(MR)方法,探索炎症蛋白因子与直肠癌风险之间的因果关系,为直肠癌的预防和治疗提供新的策略.方法 从全基因组关联分析(GWAS)数据集中选取与直肠癌相关... |
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| Title | 直肠癌炎症蛋白因子的遗传驱动:孟德尔随机化方法在临床预后研究中的应用 |
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