Analysis of the relationship between Hp infection and the expression of p27,CyclinD1,MMP-9 proteins and the related microRNAs and clinicpathological features in gastric cancer

ZHAO Jian; DAI Min; SUN Ran; XU Yajun

doi:10.3969/j.issn.1006-5725.2025.18.016

Abstract：Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ～Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ～Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ～Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ～Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.