Expressions And Clinical Significance Of Notch1 And IGF-1 In Different EGFR Gene Status Of Non-small Cell Lung Cancer

Background With the continuous improvement of medical level,especially in the research of molecular biology technology,people have a deeper understanding of the pathogenesis of non-small cell lung cancer,at the same time,for non-small cell lung cancer molecular targeted drug therapy,For example,the discovery of the target epidermal growth factor receptor(EGFR)is milder,especially for those with advanced lung cancer,targeted therapy has given them the gospel,and at the same time,But also makes non-small cell lung cancer drug therapy into a new era.EGFR is one of the Erb B receptor family.The receptor family has four receptors,namely EGFR(Erb B-1 or HER-1),Erb B-2(HER-2),Erb B-3(HER-3)and Erb B-4(HER-4).Mutation or overexpression of EGFR is closely related to the development of tumor.In addition,EGFR inhibitors have emerged,it is targeted at EGFR as a therapeutic effect,so the specificity is high,and efficient;EGFR inhibitors are divided into two categories: one is a small molecule tyrosine kinase inhibitor Tyrosine kinases inhibitor(TKI),and the other is monoclonal antibody(Mab),the former pharmacological effect is to block the EGFR intracellular segment tyrosine kinase domain binding to ATP,phosphorylation blocked,and further blocked The activation of the downstream signaling pathway is mainly two: MAPK and PI3 K / Akt;the pharmacological effect of the latter is competitive inhibition of EGFR receptor binding to the ligand,so that EGFR receptor dimerization blocked,and thus cut off the carcinogenic signal pathway The EGFR receptor binding to the corresponding ligand can activate the EGFR signaling pathway,promote tumor cell proliferation and normal cell transformation,inhibit cell apoptosis,accelerate tumor tissue angiogenesis,resulting in tumor cell infiltration,metastasis,and ultimately lead to tumor Happen to develop EGFR-TKI can inhibit tumor invasion and metastasis,and can improve the radiosensitivity of tumor tissue,the treatment effect is remarkable.However,the clinical discovery,EGFR-TKI treatment after a few months to produce drug resistance,so the study of which resistance mechanism has become a hot spot.Previous studies have shown that the incidence of lung cancer is closely related to the activation of the Notch1 signaling pathway,and that EGFR-TKI resistance is also not noted that Notch1 has not yet been identified,but the study found that Notch-1 is the intersection of many signal pathways in cells,And the transduction pathway downstream of the EGFR signaling pathway is likely to interact with Notch1.Studies have shown that Notch-1's tumor-promoting function is through the activation of insulin-like growth factor-1 receptor(insulin-like growth factors,IGF-1R)to play a role,but the expression of the correlation between the two The aim of this study is to explore the mechanism of Notch1 targeting drug resistance in non-small cell lung cancer,hoping to find a new breakthrough point for the study of EGFR-TKI resistance mechanism,and provide new ideas for The targeted drug therapy.Purpose The expression of Notch1 and IGF-1 in non-small cell lung cancer(NSCLC)was detected by immunohistochemistry.The expression and significance of EGFR-TKI in EGFR wild group,EGFR mutation group and EGFR drug resistance group were analyzed.Providing a new way for the targeted drug resistance research of non-small cell lung cancer.Methods The data of 85 patients with NSCLC were retrospectively analyzed according to the status of EGFR gene.They were divided into three groups: wild group,mutant group and drug-resistant group.Immunohistochemical SP method was used to detecte and analyze the expression of Notch1 and IGF-1 in 38 cases of wild group,28 cases of mutant group and 19 cases of drug-resistant groups.Results The positive rates of Notch1 and IGF-1 in non-small cell lung cancer were 26.34% and 21.05% respectively.The positive rates of Notch1 and IGF-1 in non-small cell lung cancer were 39.29% and 32.14%.The positive expression rates of Notch1 and IGF-1 in non-small cell lung cancer were 47.39% and 42.11% respectively(P<0.001).The expression of IGF-1 in the drug-resistant group was significantly higher than that in the wild group and the mutation group(P <0.001).The expression of Notch1 in the resistant group was significantly higher than that in the wild group and the mutant group,the difference was statistically significant(F = 42.003(P <0.001).The expression of IGF-1 in the resistant group was significantly higher than that in the wild group and the mutation group Group,the difference was statistically significant,F=38.179(P<0.001).With the non-small cell lung cancer pathological grade increased and the degree of differentiation decreased,The positive expression rates of Notch-1 and IGF-1 protein were increased in all three groups(P<0.05).The results showed that there was no correlation in the expression of Notch1 and IGF-1 between the wild group(r = 0.278,P = 0.091)and the mutant group(r= 0.229,P =0.241),but Notch1 was positively correlated with IGF-1 in drug-resistant groups(r = 0.685,P = 0.001).Conclusion The expression of Notch1 in EGFR-resistant group was significantly higher than that in the other two groups(P <0.05).The expression of IGF-1 in EGFR-resistant group was significantly higher than that in the other two groups The expression of Notch1 and IGF-1 in EGFR-resistant group was correlated,and there was no correlation in the other two groups.The reason of EGFR-TKI resistance in Notch1 was suggested to be related to IGF-1,And then further activation of EGFR downstream Ras / MAPK and P13 K / AKT signaling pathway to complete,suggesting that Notch1 signal expression may be important for EGFR-TKIs.