Correlations of Semaphorin3A and Doublecortin-like kinase 1 expressions in cervical cancer tissues with epithelial-mesenchymal transition and their clinical significances
Objective To observe the expressions of Semaphorin3A(Sema3A)and Doublecortin-like kinase 1(DCLK1)in cervical cancer tissues,and to explore their relationships with epithelial-mesenchymal transition and the influences on prognosis.Methods From January 2019 to January 2022,100 patients with cervical cancer underwent surgery in Linfen People's Hospital.Real-time fluorescence quantitative PCR was used to detect the relative expressions of Sema3A and DCLK1 mRNAs in the cervical cancer tissues and paracancerous tissues.The relative expressions of Sema3A mRNA ≥0.05 and DCLK1 mRNA≥3.25 were defined as high expression,and the relative expressions of Sema3A mRNA<0.05 and DCLK1 mRNA<3.25 were defined as low expression.The total protein was extracted from cancer tissues and paracancerous tissues,and the contents of N-cadherin and E-cadherin were determined by ELISA.The contents of N-cadherin≥3.29 μg/L and E-cadherin ≥3.52 μg/L were defined as high expression,and the contents of N-cadherin<3.29 μg/L and E-cadherin<3.52 μg/L were defined as low expression.The correlations of the relative expressions of Sema3A and DCLK1 mRNAs with the contents of N-cadherin and E-cadherin in cancer tissues were analyzed by Pearson correlation.The patients were followed up for one year and were divided into survival group(n=82)and death group(n=18).The age,tumor diameter,degree of differentiation,FIGO stage,depth of tumor invasion,lymph node metastasis and expressions of Sema3A,DCLK1,N-cadherin and E-cadherin were compared between two groups.Multivariate Cox regression was used to analyze the risk factors of death one year after surgery in patients with cervical cancer.Results(1)The relative expression of Sema3A mRNA and content of E-cadherin were lower in cancer tissues[0.05±0.02,(3.52±0.64)μg/L]than those in paracancerous tissues[0.32±0.09,(7.28±0.79)μg/L](t=29.286,P<0.001;t=36.982,P<0.001),and the relative expression of DCLK1 mRNA and content of N-cadherin were higher in cancer tissues[3.25±0.15,(3.29±0.57)μg/L]than those in paracancerous tissues[1.54±0.09,(1.38±0.26)μg/L](t=97.754,P<0.001;t=30.487,P<0.001).(2)The relative expression of Sema3A mRNA in cancer tissues was negatively correlated with the content of N-cadherin(r=-0.775,P<0.001),and positively correlated with the content of E-cadherin(r=0.832,P<0.001).The relative expression of DCLK1 mRNA was positively correlated with the content of N-cadherin(r=0.650,P<0.001),and negatively correlated with the content of E-cadherin(r=-0.752,P<0.001).(3)The proportions of FIGO stage Ⅱ,tumor invasion depth ≥1/2 muscle layer,lymph node metastasis,low expression of Sema3A,high expression of DCLK1,high expression of N-cadherin and low expression of E-cadherin were higher in death group(94.44%,72.22%,72.22%,88.89%,83.33%,88.89%,88.89%)than those in survival group(67.07%,39.02%,34.15%,47.56%,43.90%,45.12%,48.78%)(P<0.05),and there were no significant differences in the age,tumor diameter and the degree of differentiation between two groups(P>0.05).(4)FIGO stage Ⅱ(HR=3.281,95%CI:2.085-5.163,P<0.001),tumor invasion depth ≥ 1/2 muscle layer(HR=3.114,95%CI:1.964-4.937,P<0.001),lymph node metastasis(HR=3.813,95%CI,2.416-6.018,P<0.001),low expression of Sema3A(HR=0.280,95%CI:0.183-0.429,P<0.001),low expression of E-cadherin(HR=0.260,95%CI:0.166-0.407,P<0.001),high expression of DCLK1(HR=4.697,95%CI:3.287-6.713,P<0.001),and high expression of N-cadherin(HR=4.853,95%CI:3.351-7.028,P<0.001)were the risk factors of death one year after surgery in patients with cervical cancer.Conclusions High FIGO stage,tumor deep invasion,lymph node metastasis,low expressions of Sema3A and E-cadherin,and high expressions of DCLK1 and N-cadherin indicate a high risk of death one year after surgery in patients with cervical cancer.Low expression of Sema3A and high expression of DCLK1 would promote the process of epithelial-mesenchymal transition,and the detection of the expressions of them two in cancer tissues has a predictive value for the prognosis of cervical cancer patients.