Clinical Significance And Expression Of STAT4, Bax And C-myc In Human Non-small Cell Lung Cancer

Objective:To investigate the expression of STAT4(Signal transducer and activator of transcripton 4), Bax and c-myc in NSCLC (Non-Small Cell Lung Cancer) and normal lung tissue, and to explore their possible roles in the tumorigenesis of NSCLC or tumor invasion and metastasis. Method:40 cases of NSCLC specimenes and 20 cases of normal lung tissues were subjected to immunohistochemical staining (SP) for STAT4, Bax and c-myc. The NSCLC tissues were obtained from 40 patients undergoing lung cancer resection at the Department of Surgery, the Affiliated Hospital of Luzhou Medical College. No patients had received chemotherapy or radiation therapy before surgery. Their ages ranged from 26 to 72.Detailed clinicopathological parameters including age, gender,histological types, lymph node metastasis, degree of tumor differentiation and tumor stage are as following. Whose age<60 were 25 and≥60 were 15. Moderately differentiated and well-differentiated tumors were 28, poorly differentiated tumors were 12. The metastatic lymph node specimens were 20, while 20 specimens had no nodal metastasis performance. NSCLC tissues that belong toⅠ-Ⅱstage were 22 and that belong toⅢ-Ⅳstage were 18. There were 20 squamous carcinomas and 20 adenocarcinomas. There were 28 males and 12 females.All the specimens were dealt with formalin fixation, paraffin imbedding and section-cutting. After deparaffinage and hydration, we rinsed the sections with distilled water and soaked them in phosphate buffer saline. Then they were subjected to an antigen retrieval procedure by heating. Endogenous peroxidase activity was blocked using 3% H2O2 solution and nonspecific binding sites were blocked by incubating with goat serum. The slides were incubated with appropriate primary antibody (Rabbit anti-STAT4 Polyclonal Antibody, Mouse anti-Bax Polyclonal Antibody and Mouse anti-c-myc Polyclonal Antibody). Wait 2 hours and then wash them with PBS. The second antibody with biotin labeling were dropped to the slides and incubated. Wait 15 minutes and then wash them with PBS. After that, the slides were incubated with S-A/HRP for 15 minutes and then washed with PBS. Immunologic reaction was developed using DAB. The slides were counterstained with hematoxylin, mounted and then observed through microscope. Consider the cells whose cytoplasm or nucleus had brownish yellow matter as positive cells. The STAT4 and Bax positive signal were predominantly localized in cytoplasm. The c-myc positive signal were localized in both cytoplasm and nucleus, but predominantly in nucleus.The STAT4 was divided into 2 levels according to proportion of positive cells and colour depth of each slice.The Bax and c-myc were divided into 4 levels according to proportion of positive cells and colour depth of each slice. Results:(1) The expression of STAT4, Bax and c-myc in NSCLC are higher than that in normal lung tissues.The above two have a remarkable significance (P <0.01).The latter has a significance (P<0.05). (2) The expression of STAT4 in NSCLC is concerned with the histological types, and it in adenocarcinoma was significantly higher than in squamous cell carcinoma (P<0.01). The expression of Bax in NSCLC are concerned with the lymph node metastasis and tumor stage,and they inⅢ-Ⅳstage and having lymph node metastasis were significantly higher than inⅠ-Ⅱstage and not having lymph node metastasis(P<0.01). The expression of c-myc in NSCLC wasn't relation with the patient's sex, degree of tumor differentiation, lymph node metastasis, degree of tumor,histological types and age (P>0.05).(3)There were not correlations between the expressions of STAT4 and Bax (r=0.091, P=0.728, P>0.05),STAT4 and c-myc (r=-0.157, P=0.548, P>0.05) and Bax and c-myc (r=0.443, P=0.075, P>0.05) respectively. Conclusion:(1) The expressions of STAT4 protein, Bax protein and c-myc protein in NSCLC were higher than normal lung tissue. We could indicate that these three kinds of protein have participated in the formation of non-small cell lung cancer. (2) The expression of STAT4 in NSCLC was related with the the histological types, and the patient's sex, degree of tumor differentiation, lymph node metastasis, degree of tumor and age had nothing to do, indicating that STAT4 might only play a role in tumorigenesis, but not with tumor progression.The expression of Bax in NSCLC was related with the lymph node metastasis and tumor stage, and the patient's sex, degree of tumor differentiation, histological types and age had nothing to do, indicating that Bax might take part in the invasion and metastasis of the tumor. The expression of c-myc in NSCLC was not related with the patient's sex, degree of tumor differentiation, lymph node metastasis, degree of tumor,histological types and age, indicating that it may be merely a participant in the procession of the tumor. (3) The expressions of STAT4 protein and Bax protein, STAT4 protein and c-myc protein and Bax protein and c-myc protein in NSCLC were not correlated respectively, indicating they might be affected by three different ways to the occurrence and development of lung cancer.