Expression Of KiSS-1,GPR54,MMP-9 And Its Correlation With Invasive And Metastatic Potential In Non-small Cell Lung Cancer

ObjectiveInvasion and metastasis are essential characters of malignant tumors, which are responsible for cancer-related mortality of most patients who suffered from malignant tumor. Tumor metastasis is regulated and affected by multiple factors, which was previously considered involving blood supply, lymphatic drainage, machanical stimulus to primary lesion and immune status. At present, metastasis is thought to be a multi-step, multi-gene-involved process, containing invasive ability, attachment and cell-matrix interaction of malignant cells. Tumor suppressor gene(TSG) is a new hotspot of metastasis-related research. KiSS-1 is a newly cloned TSG which can inhibits tumor metastasis in several human malignancy. Metastain, KiSS-1 encoding protein can inhibit expression of matrix metalloprotein-9(MMP-9) and suppress tumor metastasis via binding to its receptor GPR54. MMP-9 is considered a vital matrix degradation enzyme which can promote tumor cell invasion and metastasis. It has been reported that KiSS-1 overexpression could inhibit tumor metastasis in various human tumors, including esophagous carcinoma, thyroid cancer and bladder cancer.Morbidity and mortality of lung cancer is increasiong gradually, and nowadays lung cancer is the leading cause of tumor-associated death. Metastasis of lung cancer to distant organs accounts for most of patient death and metastasis also influences treatment selection and prognosis judgment. Role of KiSS-1 prorein metastatin, its receptor GPR54 in invasion and metastasis of non-small cell lung cancer (NSCLC) is unclear till now. Base on this fact, the purpose of this study is to find the expression of KiSS-1,GPR54 MMP-9 in NSCLC tissues and the relation with the characteristics of invasion and metastasis.To clarify the possible relationship between KiSS-1 GPR54mRNA and MMP-9 with the invasion and metastasis of NSCLC. MethodThe study group consisted of 98 tumor tissue in non-small cell lung cancer patients and 30 normal tissue 3 cm off the tumor region. All the sample came from the patients who received the operation during 1999-2010 in People's hospital of Liaoning Province and China Medical University. All the samples were confirmed by pathologic diagnosis and the patients did not receive any radiotherapy and chemotherapy before operation.The sample were fixed with 4% neutral formalin solution, Embedded with paraffin and made into 4μm section. The expression of KiSS-1,GPR54 and MMP-9 was evaluated by immunohistochemical technique (S-P method). The PBS substituted the primary antibody as the control group.Results1.The positive expression rate of KiSS-1 in non-small cell lung cancer tissue was significantly lower than in normal lung tissue (P<0.01); meanwhile the positive expression rate of GPR54, MMP-9 in non-small cell lung cancer tissue was significantly higher than in normal lung tissues(P<0.01)2.The positive expression rate of KiSS-1 in non-small cell lung cancer with metastasis in lymph node was significantly lower than that of absence of metastasis in lymph node (P<0.05); meanwhile the positive expression rate of GPR54, MMP-9 in non-small cell lung cancer with metastasis in lymph node was significantly higher than that of absence of metastasis in lymph node (P<0.05).3.The expression of KiSS-1 and GPR54,MMP-9 in non-small cell lung cancer tissue showed a significant negative correlation.ConclustionLow KiSS-1 gene expression and high expression of GPR54,MMP-9 may play an important role in the invasion and metastasis of non-small cell lung cancer.