The relationship between the expression of IRS1 and Notch2 in colon cancer tissues and clinicopathological features and postoperative prognosis survival of patients

Fang Fang; Zhan Dahe; Pan Ting; Sun Lili; Da Shijian; Xu Rui

doi:10.3969/j.issn.1671-6450.2025.05.008

Abstract：Objective To explore the relationship between the expression of insulin receptor substrate 1(IRS1)and transmembrane receptor protein 2(Notch2)in colon cancer tissues and clinicopathological features and postoperative prognosis survival of patients.Methods A total of 95 colon cancer patients who received treatment in Oncology Depart-ment of Yueyang Central Hospital from February 2017 to July 2019 were selected,and their colon cancer tissues and para-cancer tissues were collected.Fluorescence quantitative PCR and immunohistochemical staining were used to detect the ex-pression of IRS1,Notch2 messenger RNA(mRNA)and protein;the survival and death were observed follow up for 5 years after surgery.The differences of IRS1 and Notch2 mRNA and protein in paracancer and cancer tissues were compared,and the differences of IRS1 and Notch2 mRNA in cancer tissues of colon cancer patients with different clinicopathological characteristics were compared,as well as the differences of IRS1 and Notch2 mRNA in survival group and death group.The correlation of IRS1 and Notch2 mRNA in colon cancer tissues,the relationship between IRS1 and Notch2 mRNA and 5-year survival,the factors affecting 5-year survival in patients with colon cancer,and the predictive efficacy of IRS1 and Notch2 mRNA in colon cancer tissues for 5-year survival were analyzed.Results Compared with paracancer tissues,the IRS1 mR-NA and protein positive expression rates in cancer tissues were increased,and Notch2 mRNA and protein positive expres-sion rates were decreased(t/x2/P=13.325/＜0.001,21.579/＜0.001,17.436/＜0.001,10.200/0.001).The level of IRS1 mRNA in cancer tissues in patients with TNM stage Ⅰ to Ⅱ,tumors with moderate and high differentiation,invasion depth T1 to T2,and no lymph node metastasis was lower than that in patients with TNM stage Ⅲ,low tumor differentiation,inva-sion depth T3 to T4,and lymph node metastasis,while the level of Notch2 mRNA was increased(t/P=9.565/＜0.001,4.882/＜0.001,3.199/0.002,3.335/0.001,8.112/＜0.001,6.506/＜0.001,5.925/＜0.001,4.979/＜0.001).The IRS1 and Notch2 mRNA were negatively correlated of cancer tissues(r/P=-0.603/＜0.001).5-year overall survival rate:IRS1 mRNA low expression group was higher than IRS1 mRNA high expression group[67.39％(31/46)vs 40.82％(20/49),x2/P=6.739/0.009];Notch2 mRNA high expression group was higher than Notch2 mRNA low expression group[68.18％(30/44)vs 41.18％(21/51),x2/P=6.928/0.008].Compared with survival group,IRS1 mRNA of cancer tissues in death group was significantly increased,and Notch2 mRNA was significantly decreased(t/P=4.237/＜0.001,7.086/＜0.001).TNM stage Ⅲ,low degree of tumor differentiation,invasion depth T3 to T4,lymph node metastasis and high IRS1 mRNA were the risk factors for 5-year survival of colon cancer patients,and high Notch2 mRNA was the protective factor[HR(95％CI)=2.494(1.380-4.508),2.282(1.272-4.092),2.875(1.282-6.446),2.385(1.337-4.251),3.228(1.607-6.487),0.451(0293-0.692)].The area under curve of IRS1,Notch2 mRNA and their combined prediction of 5-year sur-vival of colon cancer patients was 0.830,0.836 and 0.925,respectively,the combined prediction of the two was superior to their individual prediction efficacy(and the difference was compared using the DeLong method)(Z/P=2.240/0.025,2.099/0.035).Conclusion The IRS1 is highly expressed and Notch2 is lowly expressed in colon cancer tissues,both of which are associated with clinical pathological features and can affect prognosis,the combination of the two predicts better survival ef-ficacy within 5 years.