Expressions And Clinical Significances Of Livin And SDF-1, CXCR4, MMP-2,MMP-9in Lung Cancer

Backgroup：Lung cancer is one of the major malignant tumor that threaten to the health and life ofhuman in the world, and the metastasis of cancer is the main cause of death in patientswith lung cancer. Recent studies suggest that the overexpression of inhibitor apoptosisprotein plays an important role in the metasasis of cancer. Livin, a new member ofinhibitor of apoptosis protein(IAP) family, including two isoforms: livinαand livinβ,can inhibit cell apoptosis. SDF-1(also named CXCL12) is closely related to the invasionan metastasis of various tumor through combining chemokine receptor CXCR4. Matrixmetalloproteinase(MMPs) can degrade the extracellular matrix(ECM) to promote theinvasion of tumor cell. MMP-2and MMP-9, the majorest proteinases to degrde thecollagen IV in ECM, play an important role in the invasion and metastasis of tumor cell.Objective：To investigate the expressions and clinical significances of livin, SDF-1,CXCR4,MMP-2，MMP-9in human lung cancer, and to explore the correlations between all thesegenes.Methods：Reverse transcription polymerase chain reaction (RT-PCR) was performed to detectedthe expressions of livin, SDF-1, CXCR4, MMP-2, MMP-9mRNAs in52lung cancertissues as well as in16normal lung specimens taken from non-cancerous regions adjacentto lung cancer tissues and3benign disease lung tissues.Results：1. The positive rate of livin in lung cancer tissues84.62%（44/52）was much higher thanthose in para-cancerous18.75%（3/16）and benign disease lung tissues0%（0/3）（P=0.000，P=0.001）. The positive rates of livinαand livinβwere73.08%(38/52)and69.23%(36/52) respectively. 2. The positive rate of SDF-1in lung cancer tissues（90.38%,47/52） was much higherthan those in para-cancerous (37.50%,6/16) and benign disease lung tissues(33.33%,1/3)（P=0.000，P=0.040）. The positive rate of CXCR4in lung cancer tissues（88.46%,46/52） was much higher than those in para-cancerous (25.00%,4/16) andbenign disease lung tissues(0%,0/3)（P=0.000，P=0.003）.3. There is no difference of the expression rates of MMP-2between lung cancer tissuesand the control lung tissues(P=1.000), but the expression level of MMP-2in lungcancer tissues（1.404±0.700）was much higher than those in para-cancerous （0.798±0.554）and benign disease lung tissues（0.800±0.136）（F=7.552,P=0.001）. Thepositive rate of MMP-9in lung cancer tissues (69.23%,36/52) was much higher thanthose in para-cancerous (37.50%,6/16) and benign disease lung tissues(33.33%,1/3)(P=0.022,P=0.013）.4. The expression level of livinαin lung cancer patients that taken chemotherapy（0.4629±0.6097）was much higher that of patients who hadn’t taken chemotherapy（0.1931±0.1909）（P=0.027）.The expression level of livinβin the left lung was muchhigher than that in the right lung(P=0.030).5. The expression level of MMP-9in lung cancer tissues with lymphnode metastasis wasmuch higher than that without lymphnode metastasis（P=0.022）. The expression levelof MMP-9in lung cancer patients that taken chemotherapy (0.0863±0.1626)wasmuch lower that of patients who hadn’t taken chemotherapy(0.4520±0.5306)（P=0.003）.6. There weren’t correlations between the expressions of SDF-1, CXCR4,MMP-2andclinical characteristics (pathological types, differentiation grade, location, size,lymphnode metastasis, TNM stage, chemotherapy before operation)in lung cancertissues (all P>0.05).7. In lung cancer tissues,the expression level of livinα was positively associated withthat of livinβ（r=0.671, P=0.000）.The expression level of livinα was positivelyassociated with that of CXCR4and MMP-2in lung cancer tissues（r=0.287, P=0.039;r=0.406,P=0.003）,but the expression level of livinβ was only positively associated with that of MMP-2in lung cancer tissues（r=0.312, P=0.024）. The expression level ofCXCR4was positively associated with that of MMP-2and MMP-9in lung cancertissues（r=0.330, P=0.017；r=0.382, P=0.005）.Conclusion：Livin,SDF-1, CXCR4,MMP-2,MMP-9are highly expressed in lung caner tissues,participating the occurrence and development of lung cancer. In the lung cancer tissues,theexpression level of livinαis intimately associated with chemotherapy, and the expressionlevel of MMP-9is intimately associated with lymphnode metastasis.CXCR4is intimatelyassociated with Livinα, but doesn’t corelate to lymphnode metastasis in lung cancertissues.