The Expression Of FOXM1/FOXO3a In Non-small Cell Lung Cancer And Its Clinical Significance

Objective:To investigate the expression of the transcription factor FOXM1,FOXO3 a and its response gene CyclinD1 in non-small cell lung cancer(NSCLC)tissues and benign pulmonary lesions,and to provide a theoretical basis for the search for new molecular targets for the treatment of NSCLC.Methods: 160 patients with primary non-small cell lung cancer were selected,including80 adenocarcinomas and 80 squamous cell carcinomas.10 patients with bullae were selected.The above-mentioned patient’s diseased tissue was made into a tissue chip,and the expression of FOXM1,FOXO3 a,downstream effector protein CyclinD1 and cell proliferation index Ki-67 was detected by immunohistochemical SP method.The correlation of FOXM1,FOXO3 a,CyclinDl,Ki-67 expression and its relationship with clinicopathological features were analyzed.SPSS24.0 statistical software was used to compare the rates between the two groups using the chi-square test.The correlation between each index was analyzed using Spearman correlation.Results:1.The expression of FOXM1 in NSCLC group was significantly higher than that in benign lung disease group.The positive rate of FOXM1 in NSCLC group was 70.63%(113/160),including 72.50%(58/80)in lung adenocarcinoma and 68.75%(55/80)in lung squamous cell carcinoma,in benign pulmonary lesions.The positive rate was 20.00%.The expression of FOXM1 in NSCLC group and lung benign lesion group was statistically significant(P<0.05),but there was no significant difference in the expression of lung adenocarcinoma and lung squamous cell carcinoma(P>0.05).The expression of FOXM1 in NSCLC tissues was significantly correlated with the tumor size,and increased with the increase of tumor diameter(P<0.05),but not with the age,gender,lymph node metastasis,TNM staging(P>0.05).2.The expression of FOXO3 a in the benign lung lesions was significantly higher than that in the NSCLC group.The positive rate of FOXO3 a expression in the NSCLC group was26.88%(43/160),which was 27.50%(22/80)in lung adenocarcinoma and 26.25%(21/80)in lung squamous cell carcinoma,in the lungs.The positive rate in benign lesions was 60.00%.The expression of FOXO3 a was significantly different between NSCLC group and benign pulmonary lesions(P<0.05).However,there was no statistical difference between lung adenocarcinoma and lung squamous cell carcinoma.(P>0.05).The expression of FOXO3 a in NSCLC tissues was significantly correlated with TNM staging.The expression of FOXO3 a was significantly decreased with the increase of TNM staging(P<0.05).There was no correlation between the expression of FOXO3 a and the age,sex,lymph node metastasis,and tumor size(P>0.05).3.The positive expression rate of CyclinDl in NSCLC group was 77.50%(124/160),88.75%(71/80)in lung adenocarcinoma and 66.25%(53/80)in lung squamous cell carcinoma.The positive rate in benign lung lesions was 30.00%.The expression of CyclinDl in NSCLC and lung benign lesions,lung adenocarcinoma and lung squamous cell carcinoma showed significant differences(P<0.05).There was no correlation between age,sex,lymph node metastasis,tumor size,and TNM staging(P>0.05).In lung adenocarcinoma subgroup,the expression of CyclinDl was not significantly associated with age,sex,lymph node metastasis,tumor size,TNM stage(P>0.05).4.The positive rate of Ki-67 expression in NSCLC group was 73.75%(118/160),which was 76.25%(61/80)in lung adenocarcinoma group and 71.25%(57/80)in lung squamous cell carcinoma group.The positive rate was 40.00% in the bulla group.The expression of Ki-67 was significantly different between the NSCLC group and the bulla(P<0.05),but it was different in the lung adenocarcinoma and lung squamous cell carcinoma.No significant(P>0.05).The expression of Ki-67 in NSCLC tissues was significantly correlated with tumor size,and increased with the increase of tumor diameter(P<0.05).No correlation was found between age,sex,lymph node metastasis,and TNM staging(P>0.05).5.The expression of FOXM1 was negatively correlated with the expression of FOXO3a(r=-0.414,P<0.05).The expression of FOXM1 was positively correlated with the expression of CyclinDl(r=0.244,P<0.05).The expression of FOXO3 a was negatively correlated with the expression of Ki-67(r=-0.183,P<0.05).There was no correlation between FOXM1 expression and Ki-67 expression and FOXO3 a and CyclinDl expression(P>0.05).Conclusion:1.The expression of FOXM1 in NSCLC tissue was significantly higher than that in thebenign control group,and the tumor diameter increased and the expression level increased,suggesting that FOXM1 factor may be involved in the occurrence and development of NSCLC.It is speculated that FOXM1 may be a potential molecular target for NSCLC treatment.2.The expression of FOXO3 a in lung benign lesions was significantly higher than that in NSCLC group.With the increase of TNM stage,the positive rate of FOXO3 a expression was significantly decreased,and the expression of FOXO3 a was negatively correlated with tumor cell proliferation index,suggesting that FOXO3 a may be involved in the development of NSCLC.Is a protective factor,the occurrence of NSCLC may be related to the loss of FOXO3 a factor.3.There was a significant negative correlation between the expression of FOXM1 and FOXO3 a,and there was a positive correlation between FOXM1 and CyclinDl expression.This suggests that FOXO3 a may reverse the activity of FOXM1,a downstream effector gene,and induce the expression of CyclinDl downstream of FOXM1,which is related to the occurrence and development of NSCLC.