| Background and objectiveLung cancer?LC?is the world's highest morbidity and mortality of tumor and its pathological types were divided into small cell lung cancer?SCLC?and non-small cell lung cancer?NSCLC?and NSCLC accounted for about 85%of the above[1,2]in NSCLC lung Adenocarcinoma has more than Squamous cell carcinomas in lung cancer the first[1,2].A large amount of data show that a large proportion of lung cancer at the time of diagnosis has been late,and the first-line chemotherapy regimens for advanced lung cancer the median progression-free surial?PFS?only about 5 months[3],patients with poor prognosis.In recent years,molecular targeted drugs in the treatment of patients with advanced NSCLC has obtained the satisfactory curative effect,brought new hope for patients with lung cancer,especially the epidermal growth factor receptor,EGFR)sensitive mutations in patients with NSCLC of epidermal growth factor-complex amino acid kinase inhibitors?epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI?in the treatment of 5080%efficient[4-5].However,the study found that as the treatment continued,almost all TKI sensitive patients eventually showed the drug tolerance,which greatly reduced the expected survival time of the patients.Therefore,it can be found that drug resistance and three generations of drugs can be found in time,which has a great impact on the prognosis of patients.At present,the clinical judgment of drug resistance is still a regular CT monitoring of the lack of serological monitoring indicators,which not only brings a lot of radiation to patients but also has hysteresis.Vascular endothelial growth factor,VEGF is a kind of homologous dimers glycoprotein,with high biological activity,the proliferation of vascular endothelial cells can be stimulated strongly,the strongest endothelial growth factor is known,a large number of studies have shown that their new students to participate in a variety of solid tumors vessels[6].VEGF in addition to stimulate the growth of endothelial cells,but also can increase the permeability of blood vessels,the function is closely connected with the transfer of tumor cells[6],at the same time,the increase of the serological levels are thought to be associated with poor prognosis of tumor is closely related to the[7,8].Studies have shown that serum VEGF is closely related to lung cancer[9],but there are few studies on the relationship between VEGF and EGFR.This study by adopting the method of ELISA detection in different periods of the TKI drugs in patients with the change of serum VEGF,explore its efficacy judgment EGFR mutation sensitive patients use TKI and diagnostic value of resistance,and analyzes its associated with tumor markers CEA,NSE and tumor clinical indicators?age,sex,tumor stage,distant metastasis,tumor diameter,number of lesions?.MethodFrom January 2016-December 2016 lung adenocarcinoma EGFR sensitive patients in our hospital diagnosed 144 cases of TKI,according to the different time of taking drugs patients are divided into treatment group?31 cases?,treatment 13months group?25 cases?,treatment 46 months group?19 cases?,treatment 712month group?25 cases?,treatment resistant group?24 cases?and drug therapy for more than 1 years without resistance group?20 cases?.The use of ELISA and chemiluminescence detection of serum VEGF,CEA and NSE levels,compared to observe the differences of serum VEGF,CEA and NSE in different period of time and medication,analysis of serum VEGF and tumor markers CEA,NSE and tumorrelated clinical parameters?age,gender,tumor stage,metastasis,tumor diameter number and the relationship between the lesions?.Result1.General clinical data of patientsThere was no difference in age and sex between the 6 groups.2.The mean and comparison of serum VEGF between 6 groups of patientsNo medicine group serum concentration?729.58±103.24?pg/ml,treatment 13months group concentration?546.61±26.20?pg/ml,treatment 46 months group?543.84±26.59?pg/ml,treatment 712 months group?630.36±31.85?pg/ml,drug resistance group?773.90±87.26?pg/ml.Take medication for more than 1 years without resistance group?585.91±54.17?pg/ml;drug resistance group,serum VEGF level is the highest,no medicine group serum concentration high,no statistical difference?P>0.05?;taking the early 13 months group and 46 months group serum VEGF concentration was lowest,significantly decreased than that without medication group,and the difference was statistically significant?P<0.05?,712 group increased serum concentration after early,and there is significant difference?P<0.05?;drug resistance group is lower than the level of medication is not all resistance group increased obviously,and the No statistical difference?P<0.05?,slightly higher than the untreated group,no statistically significant difference?P>0.05?;drug therapy for more than 1 years without resistance group,serum VEGF level and all medication without resistance group level in 1 years,no statistically significant difference?P>0.05?,lower than the unexposed group and resistance group level there were significant differences?P<0.05?.3.The comparison of the mean serum CEA and NSE values between the 6 groups and the relationship with the serum VEGFThe mean serum CEA:no medicine group serum concentration?43.65±79.03?ng/ml,treatment 13 months group concentration?82.44±152.80?ng/ml,treatment46 months group?12.13±9.34?ng/ml,treatment 712 months group?8.12±8.06?ng/ml,medication resistant group?113.29±410.78 ng/ml?,medication is not morethan 1 years of resistance group?8.27±7.89?ng/ml;The mean serum NSE:no medicine group serum concentration?6.64±4.12?ng/ml,treatment 13 months group concentration?4.73±2.13?ng/ml,treatment 46months group?4.30±1.91?ng/ml,treatment 712 months group?7.01±3.11?ng/ml,medication resistant group?4.88±2.55 ng/ml?,medication is not more than 1 years of resistance group?5.85±2.23?ng/ml;No significant differences between 6 groups in the serum level of CEA?P>0.05?,the serum level of NSE in 46 months group was significantly different from the 712 month group?P<0.05?,but the measured values were within the normal reference range,the other group showed no significant difference?P>0.05?;there was no correlation between serum VEGF and serum CEA NSE?CEA:r=0.032 P>0.05;NSE:r=0.147 P>0.05?.4.The relationship between serum VEGF and tumor clinical related indexesThere was no correlation between serum VEGF and sex,age,tumor stage,tumor diameter and number of lesions in 144 cases of lung adenocarcinoma patients taking TKI drugs?P>0.05?,which was correlated with distant metastasis?P<0.05?.49 patients with no distant metastatic lung adenocarcinoma were higher than the VEGF average rate of 26.53%,and 95 patients with distant metastasis were 60%.It is obvious that patients with distant metastases are higher than the average serum VEGF concentration ratio higher than those without distant metastasis.Conclusion1.VEGF involved in the mechanism of TKI killing tumor cells and the resistance mechanism of TKI,and is expected to become a serological indicator for monitoring TKI efficacy and determining TKI resistance.2.For patients with advanced lung cancer,CEA and NSE can not be a serological indicator to judge the drug resistance of class TKI. |
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