The Expression Of CXCR4and MMP-9and Clinical Significance In Non-small Cell Lung Cancer

Objective: Lung cancer, which is the main cause of cancer deaths both inAsia and in Western populations,is the most common malignant tumor.Inrecent decades, the incidence and mortality of lung cancer is rapidly risingworldwide, especially in developed countries. Some reports indicated that theincidence and mortality of lung cancer were in the top place in our country,and the trend of the incidence was younger and younger.Statistics fromBeijing Municipal Health Bureau show that the incidence of cancer amongmen with Beijing household registration was in the first place, the secondhighest among women in2010, only second to breast cancer.In ten years from2001to2010, the incidence rate of lung cancer in Beijing increased by56%.One out of five in the new cancer patients got lung cancer.Lung cancer can bedivided into two categories: non-small cell lung cancer (NSCLC),more than80%accounts in all lung cancers,and small cell lung cancer (SCLC). Non-small cell lung cancer is often transferred to the regional lymph nodes, liver,contralateral lung,brain and bone marrow.The majority of patients sufferingnon-small cell lung cancer died of metastasis.Inhibition of non-small cell lungcancer is considered to be an important treatment strategy, thus themolecules,which is involved in metastasis of lung cancer,may become a newtarget for the treatment of non-small cell lung cancer.The chemokines，also known as chemotactic cytokines,is a class ofsmall molecule peptides with strong activation and chemotaxis for variety ofleukocyte subpopulations and non-hematopoietic cells. Stromal cell-derivedfactor-1(SDF-1),widely and constitutively expres-sed in a variety of cells andtissues,is a kind of chemo-attractant protein of CXC class,produced by bonemarrow. Chemokine receptor4(CXCR4) is one of the seven-trans-membranedomain (7TM) G-protein coupled receptor superfamily members (GPCRs). CXCR4binding with its only ligand SDF-1constitutes SDF-1/CXCR4biology axis,which plays an important role in embryonic development,mobilization and homing of hematopoietic stem cells mediated by the immuneand inflammatory response, angiogenesis,HIV infection and other fields. Moreand more evidence shows that the SDF-1/CXCR4biological axis acts as animportant role in the process of invasion and metastasis in non-small cell lungcancer.Matrix metallo-proteinases (MMPs) are a group of large family of zinc-containing proteolytic enzymes with proteolytic function,which is responsiblefor the degradation of extracellular matrix (ECM) components, in the normaltissue remodeling and repair process, including basement membrane collagen,and the excessiveness or inappropriate expression of matrix metallo-proteinaseis the main mechanism to cause invasion and metastasis in cancer tissue.Matrix metalloproteinase-9(MMP-9),the largest molecular weight enzyme inMMPs family,is one of the key enzymes in the degradation of extracellularmatrix (ECM),which can degrade the main component IV, type V collagen andgelatin in the destruction of the ECM,and type IV collagen has a closerrelationship with tumor invasion and metastasis. Research has confirmed thatMMP-9,highly expressed in head and neck cancer, esophageal cancer, stomachcancer, liver cancer, non-small cell lung cancer, breast cancer organization,isclosely related to tumor invasion and metastasis.In this study,immuno-histochemistry method was used to analyse theexpression of CXCR4and MMP-9in NSCLC and normal lung tissue (5cmabove the edge of the cancerous tissue) and the relationship between theclinical indicators,and that would provide new evidence for the invasion andmetastasis of NSCLC mechanisms and provide new approaches to thediagnosis, treatment and prognosis in NSCLC.Materials and methods: Non-small cell lung cance tissue samples of71patients, treated in Department of Thoracic Surgery in the Hebei MedicalUniversity Fourth Clinical Hospital from September2010to January2013,were selected.The inclusion criteria were as follows:confirmed by surgical resection；no chemotherapy before surgery; postoperative pathologicresults were confirmed.Another cases of adjacent normal lung tissue samples(5cm above the edge of the cancerous tissue) were as the control group.Gender, age, histological type,degree of differentiation, lymph nodemetastasis,TNM stage and other clinical data of the patients were recorded.Immuno-histochemical S-P by Three-step method was used to detect theexpression levels of CXCR4and MMP-9in the experimental group and thecontrol group specimens. Application SPSS13.0statistical software was fordata analysis in the study,statistical analysis for the relationship betweenCXCR4,MMP-9and ovarious clinical features of NSCLC by chi-square test.Spearman rank correlation analysis was used in the relationship betweenCXCR4and MMP-9. P<0.05was considered statistically significant.Results:1CXCR4in immunohistochemistry: CXCR4expression levels of71NSCLC tissues and20normal lung tissue were tested by immuno-histochemical staining. The positive rate of NSCLC group is60.6%（43/71）,and the normal lung tissue group is10%（2/20）.Statistical analysis showsthat CXCR4expression in NSCLC group was significantly higher than thenormal lung tissue group （χ2=15.96，P=0.00＜0.05）.CXCR4expressionin NSCLC tissues has nothing to do with patients`age,gender(P>0.05), buthas correlated with the degree of differentiation, TNM stage, histological typeand lymph node metastasis correlation (P<0.05).2MMP-9in immunohistochemistry: MMP-9expression levels of71NSCLC tissue and20normal lung tissue were tested by immuno-histochemical staining. The positive rate of NSCLC group is67.6%（48/71），while the normal lung tissue group is15%（3/20）.Statisticalanalysis shows that MMP-9expression in NSCLC group was significantlyhigher than in normal lung tissue group(χ2=17.52，P=0.00＜0.05).MMP-9expression in NSCLC tissues has nothing to do with patients`age, gender,(P>0.05),but has correlation with the degree of differentiation, TNM stage. patho-logical type and lymph node metastasis(P<0.05). 3Interrelationship between CXCR4and MMP-9in NSCLC: Spearmanrank correlation analysis shows:CXCR4and MMP-9in NSCLC has positivecorrelation, r=0.550，P＜0.05.Conclusion:1Positive expression of CXCR4in NSCLC increased significantlycompared with normal lung tissue next to the cancer,and also had nothing todo with patients’ age, gender but related with the degree of differentiation,TNM stage,histological type and lymph node metastasis. The expression ofCXCR4increased along with the TNM staging; The expression in lymphnode metastasis group was significantly higher than that without lymph nodemetastasis.It indicates prompt abnormal CXCR4expression is correlated withlymph node metastasis in NSCLC, and it plays an important role in theprocess of metastasis of lung cancer.2MMP-9positive expression in NSCLC increased obviously, comparedwith normal lung tissue next to the cancer and had nothing to do with patient’sage, gender, but correlated with the degree of differentiation,TNM stage,pathological type,and lymph node metastasis. The expression of MMP-9increased along with the TNM staging; the expression in lymph nodemetastasis group was significantly higher than that without lymph nodemetastasis.It suggests that the upregulation of expression of MMP-9canpromote lymph node metastasis in NSCLC, which plays an important role inthe process of metastasis of lung cancer.3Expression of CXCR4and MMP-9was positively correlated bothupregulated and the NSCLC TNM staging and lymph node metastasis in thelung tissue. It might be speculated that CXCR4and MMP-9have a synergisticeffect in the development and lymph node metastasis in NSCLC.