Expression And Significance Of HMGB1,NF-κBp65 And MMP-9 In Non-small Cell Lung Cancer

Objective:The lung cancer is one of the most common malignant neoplasms in the world. For the past few years, its morbility has got raised up. The predominant reason depends on its invasive and metastasis. High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions. It is involved in invasion and metastasis in various human malignancies. In our study, we analyzed the protein expression of HMGB1 and N F-KBp65 in 95 non small cell lung cancer (NSCLC) tissues by immunohistochemistry Our aim is to investigate the correlation between the expression of the two factors and clinical significance in NSCLC and study their roles in invasion and metastasis of NSCLC.Methods:95 cases paraffin-embeded NSCLC samples were analyzed and 27 normal lung tissues near the cancer were also studied as controls. All subjects were taken fro-m the patients who admitted for operative treatment in the Tianjin Chest Hosptial from 2007.7 to 2009.7. The expression of HMGB1,NF-KBp65 and MMP-9 protein were detected by immunohistochemical staining. We observed their expression to explore the influence on tumor matastasis, their mutual relationship, the relationship with the·clinicopathologic parameters. Data were Performed with SPSS 13.0 software.Chi-square test, fisher'exact test of Probabilities and Spearman rank correlation were used, and Staticsly significant level was considered as "alpha equals 0.05".Results:1. The expression of HMGB1,NF-KBp65 and MMP-9 protein in NSCLC.(1) The expression rates of HMGB1,NF-KBp65and MMP-9 protein in NSCLC are 48.4%,44.2% and47.4%;In the normal tissues are 25.9%,22.2% 18.5%..Significant difference were found for HMGB1,NF-KBp65 and MMP-9 expression.(2) The expression of HMGB1 in metastasis group (65.5%) was significantly higher than non-metastasis group(21.6%,.P<0.01); the expression of NF-κB p65 in non-metastasis group(21.6%) was significantly lower than metastasis group (58.6%, P<0.01); the expression of MMP-9 in non-metastasis group(27.0%) was significantly lower than metastasis group (60.3%,P<0.01) 2. The relationship between the expression of HMGB1,NF-KBp65 and MMP-9 protein with the clinicopathologic parameters of NSCLC.(1)The expression of HMGB1 protein has significant correlation to tissue typing, clinical classification and clinical stage (P<0.05 or P<0.01), but it has no correlat-ion to age,sex and tumor size (P> 0.05).(2) The expression of NF-KBp65 protein has significant correlation to tissue typing, clinical classification and clinical stage (P<0.05 or P<0.01), but it has no correlate-ion to age,sex and tumor size (P> 0.05).(3) The expression of MMP-9 protein has significant correlation to tissue typing, clinical classification and clinical stage (P<0.05 or P<0.01), but it has no correlate-ion to age,sex and tumor size (P> 0.05).3. The correlation among the expression of HMGB1,NF-KBp65 and MMP-9 in NSCLC tissues.Spearman rank correlation analysis showed that the expression of HMGB1 had obviously positive correlation with the expression of NF-KBp65 (r=-0.443, P<0.05) and MMP-9 (r=8.794, P<0.05);There was obviously positive correlation between NF-KBp65 and MMP-9(r=0.217, P<0.05).Conclusion:1. The positive rate of HMGB1 protein expression is higher in tumor and interstitial cell than that in the normal tissues. And the postitive expression rate of HMGB1 is significantly higher in the lymph node metastasis group than in the non-lymph node metastasis group. These data predicted that HMGB1 expression is a determinant of cellular invasiveness and metastasis in non-small lung cancer.2. The positive expression of NF-κBp65 and MMP-9 have significant correlation to tissue typing,clinical classification and clinical stage. And the postitive expression rate of them is significantly higher in the lymph node metastasis group than in the non-lymph node metastasis group. This might thoroughly illustrate that NF-KBp65 and MMP-9 are significant factors for the formation, development and metastasis of NSCLC. They can promote tumor metastasis as an important transcription factors.3. The expression of HMGB1 had a positive correlation with the expression of NF-κB p65 and MMP-9 in NSCLC tissues. Both expression of the three factors are obvious -sly associated with NSCLC invasion and metastasis. The results indicate that HMGB1 plays some role in suppression of the metastasis of NSCLC, which may be through activating the expression of NF-KBp65 and MMP-9.4. The detection of HMGB1 together with NF-KBp65 and MMP-9 is worth for judging lung cancer invasion and metastasis. And this may serve as prognostic indicators and guide the clinical treatment.