视网膜母细胞瘤患者TIMP-1、HIF-1α表达及其与MMP-9、VEGF的相关性研究OA

Objective:To investigate the expression levels of tissue inhibitor of metalloproteinase-1(TIMP-1)and hypox-ia-inducible factor-1α(HIF-1α)in children with retinoblastoma(RB),and to analyze their respective correlations with ma-trix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF).Methods:A total of 83 RB children,30 children with benign ophthalmopathy,and 80 healthy children who underwent routine physical examination were enrolled as RB group,benign ophthalmopathy group,and control group,respectively,from March 2018 to January 2025.The serum levels of TIMP-1,HIF-1α,MMP-9,and VEGF in the three groups were measured and compared.The relationships between these serum markers and clinicopathological charac-teristics of RB patients were analyzed.Receiver operating characteristic(ROC)curves were constructed to evaluate the diag-nostic value of these serum markers for predicting RB occurrence.Pearson correlation analysis was performed to examine the correlations among the serum levels of the four markers.Furthermore,in RB patients who received clinical intervention,the serum levels of TIMP-1,HIF-1α,MMP-9,and VEGF were compared before and after treatment.Results:The levels of ser-um TIMP-1,HIF-1α,MMP-9 and VEGF in RB group were higher than those in benign ophthalmopathy group and control group(P<0.05).Among children with different clinical characteristics,the serum levels of TIMP-1,HIF-1α,MMP-9,and VEGF were as follows:stage D/E>stage C>stage A/B(according to the International Intraocular Retinoblastoma Classification,IIRC);undifferentiated type>differentiated type;post-laminar invasion>pre-laminar invasion>no invasion(optic nerve invasion);and diffuse invasion>focal invasion>no invasion(choroidal invasion)(all P<0.05).The area under the ROC curve(AUC)of the combined detection of serum TIMP-1,HIF-1α,MMP-9,and VEGF for predicting RB occurrence was 0.863,which was significantly greater than that of each single marker alone(0.726,0.761,0.703,and 0.766,respectively;all P<0.05).The results of Pearson correlation analysis showed that in RB children,serum TIMP-1 level was positively correlated with HIF-1α,VEGF,and MMP-9 levels,and HIF-1α level was positively correlated with MMP-9 and VEGF levels(all P<0.05).Furthermore,compared with the levels before treatment,the serum levels of TIMP-1,HIF-1α,MMP-9,and VEGF in the RB group significantly decreased after treatment(P<0.05).Conclusion:The serum levels of TIMP-1,HIF-1α,MMP-9,and VEGF significantly increase in children with RB,and the magnitude of elevation is positively correlated with tumor staging,degree of differentiation,and invasive pathological characteristics.Sig-nificant positive correlations are observed between any pair of these serum markers.Combined detection of the four markers improves diagnostic efficacy for RB.However,the specificity of this combined approach is low,limiting its utility as an inde-pendent screening tool.Its clinical value lies primarily in its role as a diagnostic aid and in risk stratification.