摘要
目的探讨Toll样受体4/丝裂原活化蛋白激酶(TLR4/MAPKs)信号通路在炎性肠病(IBD)-结直肠癌中的表达差异性及对病情进展的预测价值。方法采用前瞻性方法,按照1:1:1选取2021年9月至2023年6月南阳市第二人民医院收治的91例IBD(IBD组)、91例IBD相关性上皮内瘤变(瘤变组)和91例IBD相关性结直肠癌(结直肠癌组)患者纳入研究。比较三组患者组织样本和血清中的TLR4/MAPKs信号通路相关因子[TLR4 mRNA、丝裂原活化蛋白激酶(ERK)1/2 m RNA、p38MAPK m RNA]表达水平,多因素Logistic回归分析血清TLR4/MAPKs信号通路对IBD病情进展的影响,采用受试者工作特征(ROC)曲线、曲线下面积(AUC)分析血清TLR4/MAPKs信号通路对IBD病情进展的预测价值。结果结直肠癌组患者组织标本TLR4 m RNA、ERK1/2 mRNA、p38MAPK m RNA表达水平分别为1.84±0.47、1.60±0.38、2.02±0.57,明显高于瘤变组的1.36±0.31、1.15±0.32、1.53±0.40和IBD组的1.02±0.25、0.86±0.20、1.13±0.29,差异均有统计学意义(P<0.05);结直肠癌组患者血清TLR4 mRNA、ERK1/2 mRNA、p38MAPK m RNA表达水平分别为1.14±0.36、1.03±0.25、1.35±0.42,明显高于瘤变组的0.78±0.25、0.62±0.30、0.94±0.28和IBD组的0.56±0.17、0.40±0.12、0.61±0.20,差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,血清TLR4 m RNA、ERK1/2 m RNA、p38MAPK m RNA升高是IBD病情进展的独立影响因素(P<0.05);ROC曲线分析结果显示,血清TLR4 m RNA、ERK1/2 m RNA、p38MAPK mRNA联合预测IBD相关性上皮内瘤、结直肠癌的AUC分别为0.900、0.932,明显优于各指标单独预测(P<0.05)。结论IBD相关结直肠癌患者血清和组织中TLR4/MAPKs信号通路相关因子表达上调,与IBD病情进展密切相关,血清TLR4/MAPKs信号通路相关因子TLR4m RNA、ERK1/2 m RNA、p38MAPK m RNA可用于辅助预测IBD病情进展。
Objective To investigate the differential expression of the Toll-like receptor 4/mitogen-activated protein kinase(TLR4/MAPKs)signaling pathway in inflammatory bowel disease(IBD)-colorectal cancer,and to evaluate its predictive value for disease progression.Methods A prospective approach was used,91 patients with IBD(IBD group),91 patients with IBD-associated intraepithelial neoplasia(neoplasia group),and 91 patients with IBD-associated colorectal cancer(colorectal cancer group)admitted to Nanyang Second General Hospital from September 2021 to June 2023 were consecutively enrolled at a ratio of 1:1:1.The expression levels of TLR4/MAPKs signaling pathway-related factors(TLR4 mRNA,extracellular signal-regulated kinase[ERK]1/2 mRNA,p38MAPK mRNA)in tissue samples and serum of the three groups of patients were measured and compared.Multivariate logistic regression analysis was conducted to assess the impact of the serum TLR4/MAPKs signaling pathway on the progression of IBD,and receiver operating characteristic(ROC)curves and area under the curve(AUC)were used to analyze the predictive value of the serum TLR4/MAPKs signaling pathway for IBD progression.Results The expression levels of TLR4 mRNA,ERK1/2 mRNA,and p38MAPK mRNA in tissue specimens from patients in colorectal cancer group were 1.84±0.47,1.60±0.38,and 2.02±0.57,respectively,which were significantly higher than corresponding 1.36±0.31,1.15±0.32,and 1.53±0.40 in the neoplasia group and corresponding 1.02±0.25,0.86±0.20,and 1.13±0.29 in the IBD group,with statistically significant differences(all P<0.05).Similarly,the expression levels of serum TLR4 mRNA,ERK1/2 mRNA,and p38MAPK mRNA from patients in colorectal cancer group were 1.14±0.36,1.03±0.25,and 1.35±0.42,respectively,which were higher than corresponding 0.78±0.25,0.62±0.30,and 0.94±0.28 in the neoplasia group and 0.56±0.17,0.40±0.12,and 0.61±0.20 in the IBD group,with statistically significant differences(all P<0.05).Multivariate logistic regression analysis showed that elevated serum levels of TLR4 mRNA,ERK1/2 mRNA,and p38MAPK mRNA were independent factors influencing the progression of IBD(P<0.05).ROC analysis demonstrated that the combined detection of serum TLR4 mRNA,ERK1/2 mRNA and p38 MAPK mRNA yielded AUCs of 0.900 for predicting IBD-associated intraepithelial neoplasia and 0.932 for predicting IBD-associated CRC,both significantly superior to the predictive performance of each marker alone(P<0.05).Conclusion The up-regulation of TLR4/MAPKs signaling factors in both serum and tissue of patients with IBD-associated colorectal cancer closely correlated with the progression of IBD,and the serum levels of TLR4 mRNA,ERK1/2 mRNA,and p38MAPK mRNA can serve as auxiliary biomarkers for predicting the progression of IBD.
作者
刘源
侯楠
高俊
赵迪
LIU Yuan;HOU Nan;GAO Jun;ZHAO Di(Department of Gastrointestinal Oncology,Nanyang Second General Hospital,Nanyang 473000,Henan,CHINA)
出处
《海南医学》
2025年第11期1526-1530,共5页
Hainan Medical Journal
基金
2022年河南省医学科技攻关联合共建项目(编号:LHGJ20222047)。
关键词
炎性肠病
结直肠癌
Toll样受体4/丝裂原活化蛋白激酶信号通路
组织
血清
病情进展
Inflammatory bowel disease
Colorectal cancer
Toll-like receptor 4/mitogen-activated protein kinase signaling pathway
Tissue
Serum
Disease progression
