Diagnostic And Prognostic Of HE4 In Serum And Pleural Fluid Of Lung Cancer

Objective: Evaluate the diagnostic and prognostic significance of human epididymis protein 4(HE4)level in serum and pleural fluid with lung cancer patients.Method: 1.Collect serum and pleural fluid specimens from lung cancer patients and collect serum control group.2.Measure the level of HE4 in serum and pleural fluid by enzyme immune assay(ELISA)to each group.3 Gather up the clinical data of 83 cases of patients with lung cancer and 31 cases of patients with pleural fluid,including the patient's gender,age,pathological type,clinical stage,smoking index,KPS score,response to treatment,lymph node metastasis and expression of Ki-67 and CEA,SCC,NSE,CYFRA21-1 with patients before treatment and through looking up cases of outpatient service,the methods of telephone follow-up of patients with PFS and OS time.The last follow-up time is February 27,2017.Using SPSS16.0 software to analyze the experimental data.Result: 1.Serum HE4 of lung cancer patients before treatment concentration is199.08(126.17,294.71)PM,healthy people group serum HE4 concentration at 58.66(46.66,76.10)PM,the before treatment of patients with lung cancer serum HE4 concentration significantly higher than the healthy group,the difference is statistically significant(P < 0.05).2.With pathology as the gold standard,draw a ROC curve before treatment serum HE4 diagnosis of lung cancer,the area under the curve is 0.946,serum HE4 can be used in the differential diagnosis of lung cancer,the difference is significant(P < 0.05);When the content of serum HE4 116.94 PM,obtain the best specific degrees and sensitivity,79.5% and 96.8%,respectively.3.The expression level of serum HE4 before treatment of patients is related to clinical staging,KPS score,lymph node metastasis(P < 0.05),but with age,sex,smoking index,pathological type,the expression of Ki-67 are unrelated(P > 0.05),but adenocarcinoma of lung cancer is significantly higher than other pathological types.4.83 cases of patients with lung cancer in PFS is 5.98(95%CI 4.73-7.23)months.Ki-67,KPS score,treatment response and high levels of serum HE4(> 150 pmol/L)and high levels of serum CEA(> 50 ng/ml)in patients with lung cancer are single factor for PFS(P < 0.05),through the Log-Rank test results show that the low HE4 group(< 150 pmol/L)in patients with an average time of PFS is 8.30(95% CI 6.09 10.50)months,is significantly higher than high level HE4 groups 4.35(95% CI 3.30-5.41)months.5.83 lung cancer patients,on average,overall survival(OS)is 10.28(95% CI 8.49-12.06)months,Ki-67,smoking index,KPS score and two groups of high levels of serum HE4(> 117 pmol/L;> 150 pmol/L),high levels of serum CEA(> 50 ng/ml)and high levels of serum keratin 19 fragment(> 10 ng/ml)are single factor for overall survival(OS)time(P < 0.05),through the Log-Rank test results show that the low HE4 group(< 150 pmol/L)in patients with an average survival time was 13.51 months(95% CI,10.36-16.67),significantly higher than high level HE4 groups 7.70(95% CI,6.26-9.14)months6.With single factor affecting overall survival factor P value is less than 0.05 for the selected factors,multiple factors regression analysis,according to Cox multiple factors regression analysis shows that the response to treatment(HR = 2.606),KPS score(HR = 0.400),high levels of serum HE4(> 150 pmol/L)(HR = 1.726),high level CYFRA21-1(> 10 ng/ml)(HR = 2.140)are independent prognostic factors in patients with lung cancer(P < 0.05).7.Lung cancer with pleural effusion,the median concentration of HE4 is 956.57 PM,interquartile range interval is(652.49-1128.78)PM.Pleural effusion by Spearman correlation analysis researching HE4 expression is only related to expression of Ki-67(r = 0.399,P < 0.05),while in age,sex,smoking index,pathological type,clinical stage,distant metastasis are not associated with pleural HE4 expression(P > 0.05).8.31 cases of lung cancer patients with pleural effusion,an average survival is 11.58(95% C 7.61-15.55)months.Using single factor analysis of risk of Cox regression model,pleural HE4 values(cut-off point 600,800,1000)is not single factor lung cancer patients' overall survival time(P>0.05),through the Log-Rank test results show that in 800 pmol/L for cutoff point,high and low risk,low of HE4 group of patients with an average survival time is 14.63(95% CI 8.04-21.23)months,with high HE4 group is significantly higher than 9.37(95% CI 4.61-14.12)months.9.18 cases of lung cancer patients,HE4 of in pleural effusion is significantly higher than serum,the difference is statistically(P = 0.019),but both have no obvious correlation(r = 0.0.391,P = 0.391).Conclusion:1.Before treatment of patients with lung cancer serum HE4 concentration significantly higher than that of healthy people,maybe used for the diagnosis of lung cancer.2.Lung cancer patients serum HE4 expression level before treatment is related to clinical staging,KPS score,lymph node metastasis(P < 0.05),but with age,sex,smoking index,pathological type,Ki-67 expression and HE4 expression are not related,,but adenocarcinoma of lung cancer is significantly higher than other pathological types.3.Ki-67,KPS score,treatment response and high levels of serum HE4 and high levels of serum CEA impact PFS in patients with lung cancer4.Ki-67,treatment response,smoking index,KPS score and high levels of serum HE4,high levels of serum CEA and high levels of serum CYFRA21-1 impact OS in patients with lung cancer5.High levels of serum HE4,high levels of serum CYFRA21-1,response to treatment,KPS score are independent prognostic factors in patients with lung cancer.6.Pleural effusion of HE4 expression is only related to expression of Ki-67,the age,sex,smoking index,pathological type,clinical stage,distant metastasis are not associated with pleural effusion of HE4 expression.7.Pleural effusion of HE4 value is not the influence factors of lung cancer patients to overall survival time,also not independent prognostic factors.8.Pleural effusion of HE4 is not associated with serum HE4 expression.