Expression And Significance Of KiSS-1,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. KiSS-1 is a new tumor metastasis-suppressor gene, whose abnormal expression is related with metastasis and prognosis of Bladder cancer,Gastric carcinoma and Breast cancer[1-4]. KiSS-1 plays a key role on inhabit-ing tumor's metastasis through interrput the binding of nuclear factor kappa B (NF-κB) and MMP-9[5]. In our study, we analyzed the protein expression of KiSS-1 and N F-κBp65 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 2006.10 to 2008.10. The expression of KiSS-1,NF-κBp65 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 SPSS13.0 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 KiSS-1,NF-κBp65 and MMP-9 protein in NSCLC.(1) The expression rates of KiSS-1,NF-κBp65 and MMP-9 protein in NSCLC are 35.4%,44.2%,47.4%;In the normal tissues are 0%,25.9%,18.5%.Significant difference was found for KiSS-1 expression but did not exist for NF-κBp65 and MMP-9.(2) The expression of KiSS-1 in non-metastasis group(59.5%) was significantly higher than metastasis group(20.7%, P<0.01).In the metastasis group, the expression of KiSS-1 protein in lymph node metastasis was markedly lower than the corresponding primary tumor(P<0.05);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 KiSS-1,NF-κBp65 and MMP-9 protein with the clinicopathologic parameters of NSCLC.(1)The expression of KiSS-1 protein has significant correlation to clinical stage (P <0.05), but it has no correlation to clinical classification,tissue typing,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 KiSS-1,NF-κBp65 and MMP-9 in NSCL-C tissues.Spearman rank correlation analysis showed that the expression of KiSS-1 had a negative correlation with the expression of NF-κBp65(r=-0.222,P<0.05).;There was obviously negative correlation nbetween KiSS-1 and MMP-9 (r=-0.312, P<0.05) expression in NSCLC;There was obviously positive correlation between NF-KBp65 and MMP-9(r=0.217, P<0.05).Conclusion:1. The positive rate of KiSS-1 protein expression is higher in NSCLC tissue than that in the normal tissues. And the postitive expression rate of KiSS-1 is significantly lower in the lymph node metastasis group than in the non-lymph node metastasis group. These data predicted that KiSS-1 abnormal expression is related with metastasis of NSCLC, and it plays important role in suppression of the metastasis of malignant neoplasms.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-κBp65 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 KiSS-1 had a negative 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 KiSS-1 plays some role in suppression of the metastasis of NSCLC, which may be through inhibiting the expression of NF-κBp65 and MMP-9.4. The detection of KiSS-1 together with NF-κBp65 and MMP-9 is worth for judging lung cancer invasion and metastasis. And this may serve as prognostic indicators and guide the clinical treatment.