Analysis The Relationship Between EGFR 19/21 Gene Mutations And STAT3 In Lung Adenocarcinoma

Objective To analysis the relationship between the epidermal growth factor receptor(EGFR) mutation in exons nineteenth or twenty-one and the expression of signal transducer and activator of transcription 3(STAT3) in lung adenocarcinoma patients, we studied their functions and clinical significances in the occurrence, development, invasion and metastasis in lung adenocarcinoma.Methods Retrospective analysis of 150 cases of pathological diagnosed with lung adenocarcinoma patients specimens, used Taqman amplification refractory mutation system(Taqman-ARMS) determinated the epidermal growth factor receptor mutation in exons nineteenth or twenty-one(EGFR 19/21) in the tumor tissues, and divided into two groups according to the results. The expression of STAT3 in tumor specimens was detected by using immunohistochemistry method. Compared the results and combined with the clinical and pathological datas to explore the relationship between them. Statistical analysis was performed using statistical package for social science statistical software package(SPSS18.0). P values<0.05 indicated statistically significant difference.Results(1) Statistical significant difference was found in the different differentiation degrees of tumor for the expression of STAT3 protein in lung adenocarcinoma(P=0.032, P<0.05).The lower differentiation degree, the higher the expression, the expression of the two was negatively correlation( r=-0.186, P<0.05).But it had a positive relationship with P-TNM staging(r = 0.256, P<0.05).In P-TNM staging, higher expression was found in Stage ? and the above Stages than Stage ?A and Stage?B. There was no statistical significant difference of the STAT3 protein in different ages, different gender groups, different size of tumor groups, different Lymph node metastasis groups and different infiltration depth groups(P>0.05).(2) STAT3 protein positive expression rate was 65.3% in the 72 patients with EGFR wild-type, while it was 76.9% in the 78 patients with EGFR mutation in lung adenocarcinoma. The positive expression of STAT3 protein in EGFR mutation group was significantly higher than that in EGFR wild-type group(H=4.618 P=0.032, P<0.05). STAT3 protein positive expression was also difference in the different exon of the EGFR gene mutations. STAT3 protein positive expression rate was 69.3% in the 36 patients with the EGFR mutation in exon nineteenth(EGFR 19), while it was 83.3% in the 42 patients with the EGFR mutation in exon twenty-one(EGFR21).The positive expression in EGFR21 mutation group was significantly higher than that in EGFR19 group(H=4.698P=0.030,P<0.05).Conclusion(1) STAT3 as a signal transmission tool, its expression may play a promoting role in the occurrence, development and invasion for lung adenocarcinoma. The expression of STAT3 in lung adenocarcinoma was related to differentiation and tumor stage. STAT3 may provide the important basis of the degree for the development, malignant degree and prognosis of lung adenocarcinoma.(2) With the positive expression of STAT3 protein in EGFR(19/21)mutation group was significantly higher than that in EGFR wild-type group, suggesting that EGFR(19/21) gene mutation expression could up-regulate the expression of STAT3 protein. EGFR and STAT3 as the cancer genes had a synergistic effection. Both of them through JAK-STAT3 signal transduction pathway played an important activation in lung cancer occurrence, development, invasion and metastasis. In non-small cell lung cancer(NSCLC) patients with the EGFR(19/21) gene mutation, EGFR-TKI could effectively block the activation of EGFR signal into cancer cells, STAT3 protein could not be activated and JAK-STAT3 signal transduction pathway could be effectively blocked, They played an important role in the anti-tumor.(3) With the positive expression in EGFR 21 mutation group was significantly higher than that in EGFR19 group, suggesting that the drug response rate(RR)with the application of EGFR-TKI(Gefitinib?Erlotinib),the EGFR21 mutation patients may be better than the EGFR19 mutation patients in the treatment of non-small cell lung cancer(NSCLC). Detection of STAT3 protein can be used as an effective judgment and predicted index before using the EGFR-TKI to treat the patients with the EGFR mutation in lung adenocarcinoma.