Expression Of FEZF1-AS1 And AKT3 In Advanced Lung Adenocarcinoma And Their Relationship With The Efficacy Of EGFR-TKIs

Objective To investigate the expression of FEZF1-AS1 and AKT3 in advanced lung adenocarcinoma（LAC）and their relationship with epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）in the treatment of EGFR mutation in advanced lung adenocarcinoma.Methods（1）Patients who visited the department of respiratory and critical care medicine in the first affiliated hospital of Bengbu medical college from July 2019 to December 2021 were collected.These patients obtained pathological tissues through B-ultrasound-guided or CT-guided percutaneous lung puncture,endobronchailultrasound（EBUS）,internal medicine thoracoscopy or fiberoptic bronchoscopy,and were diagnosed by the baseline as NSCLC by the department of pathology of our hospital.Patients with EGFR mutation（19Del,L858 R,etc.）and first-line treatment of EGFR-TKIs were included in this study,and 54 cases were finally enrolled and their first confirmd pathological wax tissues were collected.（2）Immunohistochemistry（IHC）was used to detect the expressiong of FEZF1-AS1 and AKT3 proteins in patients with EGFR mutation and their relationgship with clinical data and their correlation were analyzed.Patients were followed up in outpatient department or telephone for progression-free survival（PFS）,overall survival（OS）,short-term efficacy and adverse reactions.SPSS22.0 software was used to analyze and evaluate its relationship with the efficacy and prognosis of EGFR-TKIs.（3）Kaplan-Meier method was used to analyze the PFS and OS relationship between FEZF1-AS1 and AKT3 in advanced lung adenocarcinoma tissues and patients with advanced lung adenocarcinoma after first-line treatment with EGFR-TKIs,and the survival curve was drawn and tested by log-rank.Results（1）The positive rate of FEZF1-AS1 expression in 54 advanced lung adenocarcinoma tissues with EGFR mutation was 55.56%（30/54）,and mainly located in the nucleus.The positive rate of AKT3 expression was 51.85%（28/54）,and mainly in the cytoplasm.（2）The positive expression of FEZF1-AS1 in EGFR-TKIs resistant patients with EGFR mutation in advanced lung adenocarcinoma was not correlated with age,gender,smoking status,EGFR mutation type,distant metastasis or lymph node metastasis,and there was no statistical significance（P>0.05）.However,it was related to the degree of differentiation and TNM stage,and the differences were statistically significant（P <0.05）.（3）The incidence of drug resistance in patients with positive FEZF1-AS1 expression after EGFR-TKIs was higher than that in patients with negative expression,and the survival rate was lower,and the differences in log-rank survival curves were statistically significant（P<0.05）.（4）The positive expression of AKT3 in EGFR-TKIs resistant patients with EGFR mutation in advanced lung adenocarcinoma was not correlated with age,gender,smoking status,EGFR mutation type,distant metastasis or lymph node metastasis,and there was no statistical significance（P>0.05）.However,it was related to the degree of differentiation and TNM stage,and the differences were statistically significant（P <0.05）.（5）The incidence of drug resistance in patients with positive AKT3 expression after EGFR-TKIs was higher than that in patients with negative expression,and the survival rate was lower,and the differences in log-rank survival curves were statistically significant（P<0.05）.（6）Correlation analysis between FEZF1-AS1 and AKT3: the correlation coefficient r=0.406,indicating a positive correlation between FEZF1-AS1 and AKT3 in cancer tissues（P=0.006）.（7）In the patients with EGFR mutation and after first-line treatment with EGFR-Tk Is,the incidence of drug resistance in FEZF1-AS1 +/AKT3+ group was significantly higher than that in FEZF1-AS1-/AKT3-group,and the survival rate was significantly lower than that in FEZF1-AS1-/AKT3-group,the PFS and OS were both significantly shorter.There was significant difference in survival curves between the two groups.（P<0.05）.（8）Short-term effects: In the FEZF1-AS1 positive group,ORR was 70.00%,DCR was 86.67%,including CR 0（0.00%）,PR 21（70.00%）,SD 5（16.67%）and PD 4（13.33%）.In the FEZF1-AS1 negative group,ORR was 75.00%,DCR was 87.50%,including CR 0（0.00%）,PR 18（75.00%）,SD 3（12.50%）,and PD 3（12.50%）.There was no significant difference between ORR and DCR（χ2 was 0.019 and 0.000,P >0.05）.AKT3 positive group: ORR was 71.43%,DCR was 85.71%,CR 0（0.00%）,PR 20（71.43%）,SD 4（14.29%）,PD 4（14.29%）.In the AKT3 negative group,ORR was 73.08%,DCR 88.46%,CR 0（0.00%）,PR19（73.08%）,SD 4（15.38%）,PD 3（11.54%）.There was no significant difference between ORR and DCR（χ2 was 0.019 and 0.000,P >0.05）.（9）Adverse reactions: 22 cases（40.74%）of nausea,vomiting and decreased appetite,21 cases（38.89%）of skin toxicity（mainly rash and itching）,18 cases（33.33%）of diarrhea,and 8 cases（14.81%）of liver enzyme increase,10 cases（18.52%）of stomatitis and 1 case（1.85%）of interstitial pneumonia occurred during the treatment of 54 patients with advanced lung adenocarcinoma using EGFR-Tk Is.Conclusion（1）Both FEZF1-AS1 and AKT3 were expressed in advanced lung adenocarcinoma,and the expression intensity was different.The positive rates were55.56% and 51.85%,respectively.（2）The expression of FEZF1-AS1 and AKT3 was related to the incidence of drug resistance and overall survival after first-line targeted therapy for EGFR mutant lung adenocarcinoma.Patients with positive expression of both FEZF1-AS1 and AKT3 had a higher incidence of drug resistance,shortered PFS and OS,and their survival rates declined.（3）Detection of the FEZF1-AS1 and AKT3 expression in patients with advanced lung adenocarcinoma with EGFR mutation is of great significance in predicting the emergence of drug resistance and overall survival after first-line treatment with EGFR-TKIs,and can be used in the clinical application of EGFR-TKIs.