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Determination Of BFGF、MMP-9、TIMP-1in Patients With Lung Cancer And Their Clinical Significance

Posted on:2014-08-26Degree:MasterType:Thesis
Country:ChinaCandidate:X J WangFull Text:PDF
GTID:2254330392473166Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: The purpose of this study is to detect the serum samples of basic fibroblastgrowth factor (bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinaseinhibitors-1(TIMP-1) content in lung cancer patients and healthy people, to compare thebFGF、MMP-9、TIMP-1content difference in serum samples of lung cancer patients andhealthy people、explore their correlation with the degree of tumor differentiation、clinicalstage、distant metastasis and pathological features, to study their clinical significance of thelung cancer development.Methods:1、Collecte63copy serum samples of patients with pathologically diagnosed lung cancerpatients serum samples in Gansu People’s Hospital, the specimens of patients did not undergosurgery、chemotherapy and radiotherapy. Male33cases,30were females; age of38-78yearsold, median age was59years old, the average age was57.46±7.48years, they were dividedinto three groups:<45years16cases, aged45-65years22cases、>65years25cases;according to the pathological types,they were divided into two groups: non-small cell lungcancer group34patients (including14cases of squamous cell carcinoma,17cases ofadenocarcinoma, bronchioloalveolar carcinoma3cases), small cell lung cancer group29cases;according to the the period standards,they were divided into tinto three groups: I+II in17cases,III period20cases,IV period26cases; according to the lymph node metastasis,theyweredivided into two groups: N1+N237cases,N326cases; according to the presence oflevel the metastasis,they were divided into two groups: distant metastases26patients,withoutdistant metastases37patients; according to the degree of differentiation,they were dividedinto three groups: poorly differentiated group24cases, moderately differentiated group15 cases, well-differentiated group24cases;according to tumor size the range,they were dividedinto three groups:<3cm18cases,3cm-5cm25cases,>5cm20cases;according to smokingstatus,they were divided into two groups: the smokers39cases, non smokers24cases.The excluded conditions of patients in the trial:①patientsreceived treatment radiotherapyand chemotherapy;②COPD、asthma、pulmonary heart disease、pulmonary interstitialfibrosis patients;③c onnective tissue disease patients;④p atientswiht history of coronaryheart diseaseand diabetes.Collection43copy serum samples of healthy people as a control group in GansuPeople’s Hospital Medical Center, including23males and20females; age39-80years old,the median age was57years、average age of53.46±7.26years old, they were divided intothree groups:<45years11cases,45-65years14cases,65years old18cases; they weredivided into two groups according to smoking status: the smokers21cases,22cases ofnon-smokers.2、All lung cancer patients did not receive any treatment, fasting peripheral venous bloodcollected5ml dry sterile tube without anticoagulant. All samples were placed in thepost-acquisition room temperature30mim、2000r/min centrifuged for10minutes in2hours,and then with sterile pipette serum absorb shift on2.0ml EP tube,last code and place in therefrigerator at-80.0℃saved pending measured. The healthy control group, serum samplesfrom the Gansu Hospital Medical Center, the blood specimen extracting and processingmethod was similar as lung cancer patients. Specimen collection process should be taken toavoid repeated freezing and thawing.3、Double antibody sandwich ELISA (Enzyme-linked immunoadsorbent assay, ELISA)detection contents of basic fibroblast growth factor (bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinase inhibition factor-1(TIMP-1) of43cases in healthypeople (the control group)serum samples、63cases in patients with lung cancer (lung cancergroup) serum samples in Gansu People’s Hospital. The content of results expressed in pg/ml.4、Statistical analysis: SPSS19.0software package for statistical analysis. Measurementdata are used x±s,all datas were processed by the normal distribution and variance test of homogeneity before Statistics, in line with the t-test conditions. Using independent samplet-test between the two groups, the group was used to compare a single factor ANOVA t-test;correlation between the variables of the normal distribution analysis using Pearson correlationanalysis.All statistical tests were double The side test, P <0.05for the difference wasstatistically significant.Result:1、The serum contents of bFGF、MMP-9、TIMP-1in lung cancer patients were846.25±9.64pg/ml、598.42±21.84pg/ml、600.05±3.58pg/ml;the serum contents of bFGF、MMP-9、TIMP-1in healthy control were192.18±7.65pg/ml、548.56±19.87pg/ml、359.82±5.76pg/ml. The serum contents in lung cancer group was significantly higher than thehealthy control group, this result was statistically significant (P <0.01).2、Compare with serum contents of basic fibroblast growth factor (bFGF)、matrixmetalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitors-1(TIMP-1) in lung cancerpatients and healthy control group,according to the general clinical characteristics(age,smoking status, gender).①According to age: the serum contents of basic fibroblast growth factor (bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1) in <45years age lung cancer group were819.16+6.54pg/ml、597.76+6.61pg/ml、598.70+27.87pg/ml,the serum contents of basic fibroblast growth factor (bFGF)、 matrixmetalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1) in45-65yearsage lung cancer group were854.91+8.95pg/ml、598.54+5.85pg/ml、602.79+20.23pg/ml,theserum contents of basic fibroblast growth factor (bFGF)、 matrix metalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1) in>65years of age lung cancergroup were835.89+9.84pg/ml、601.23+3.42pg/ml、591.97+22.81pg/ml; accordance withthe different age segments grouped, comparison of serum bFGF、 MMP-9and TIMP-1in thelung cancer group was not significant difference (P>0.05).The serum contents of basic fibroblast growth factor (bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1) in <45years age healthy controlgroup were192.15+8.64pg/ml、417.78+9.78pg/m、358.37+22.67pg/m,the serum contents of basic fibroblast growth factor (bFGF)、 matrix metalloproteinase-9(MMP-9)、 matrixmetalloproteinase inhibitor-1(TIMP-1) in45-65years age healthy control group were193.04+9.64pg/ml、498.34+8.67pg/ml、354.54+18.94pg/ml, the serum contents of basic fibroblastgrowth factor (bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinaseinhibitor-1(TIMP-1) in65year old healthy control group were191.08+8.64pg/ml、521.18+4.26pg/ml、331.26+19.24pg/ml,accordance with the different age segments grouped,comparison of serum bFGF、MMP-9and TIMP-1in healthy control group was not significantdifference (P>0.05).Between the two groups,accordance with the different age segments grouped,the serumcontents of bFGF, MMP-9and TIMP-1in lung cancer patients were significantly higher thanhealthy control group (P <0.01).②According to smoking status: the serum contents of basic fibroblast growth factor(bFGF)、matrix metalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1)in lung cancer patients with smoking were851.64+9.64pg/ml、599.50+3.92pg/ml、601.21+16.12pg/ml,the serum contents of basic fibroblast growth factor (bFGF)、matrixmetalloproteinase-9(MMP-9)、matrix metalloproteinase inhibitor-1(TIMP-1) lung cancerpatients without smoking were846.16+8.65pg/ml、599.07+24.30pg/ml、595.39+6.43pg/ml,according to smoking status, comparison of serum contents of bFGF、MMP-9、TIMP-1in thelung cancer patients was no significant difference (P>0.05).The serum contents of basicfibroblast growth factor (bFGF)、 matrix metalloproteinase-9(MMP-9)、 matrixmetalloproteinase inhibitor-1(TIMP-1) in the healthy control group with smoking were192.05+5.74pg/ml、509.06+4.81pg/ml、378.28+18.02pg/ml; the serum contents of basicfibroblast growth factor (bFGF)、 matrix metalloproteinase-9(MMP-9)、 matrixmetalloproteinase inhibitor-1(TIMP-1) in healthy control group without smokingwere191.08+6.85pg/ml、498.37+18.67pg/ml、395.36+8.93pg/ml.According to smoking status,comparison of serum contents of bFGF、MMP-9、TIMP-1in healthy control group was nosignificant difference (P>0.05).Between the two groups,according to smoking status,the contents of bFGF、MMP-9、TIMP-1in lung cancer group were significantly higher than healthy control group (P <0.01). ③According to gender: male in lung cancer group, the serum contents of bFGF、MMP-9、TIMP-1were864.25+9.25pg/ml、599.50+3.92pg/ml、601.21+16.12pg/ml;femalein lung cancer group,serum contents of bFGF、 MMP-9、 TIMP-1were were862.15+7.64pg/ml、599.07+24.30pg/ml、595.39+6.43pg/ml.According to gender, comparisonof serum contents of bFGF、MMP-9、TIMP-1in lung cancer group was no significantdifference (P>0.05).Male in healthy controls, the serum contents of bFGF、MMP-9、TIMP-1were190.08+5.84pg/ml、509.06+4.81pg/ml、378.28+8.02pg/ml;female in healthycontrols,serum contents of bFGF、 MMP-9、 TIMP-1were198.14+6.25pg/ml、498.37+18.67pg/ml、395.36+8.93pg/ml.According to gender, comparison of serum contentsof bFGF、MMP-9、TIMP-1in healthy controls was no significant difference (P>0.05).Between the two groups in accordance with the gender grouped,the serum contents ofbFGF、MMP-9、TIMP-1in lung cancer group were significantly higher than healthy controlgroup (P <0.01).3、According to the pathological type: the serum contents of bFGF、MMP-9、TIMP-1innon-small cell lung cancer group were838.76±5.76pg/ml、598.76±19.76pg/ml、600.01±2.98pg/ml, the serum contents of bFGF、MMP-9、TIMP-1in small cell lung cancer groupwere841.65±9.84pg/ml、601.84±21.08pg/ml、598.81±5.76pg/ml.According to pathologicaltype, comparison of serum contents of bFGF、MMP-9、TIMP-1in lung cancer group was nosignificant difference (P>0.05).4、The relationship of between serum contents of bFGF、MMP-9、TIMP-1and clinicalpathological features in lung cancer:①Accordance with the International Cancer Alliance (UICC) staging system they weredivided into4Phase:I5cases、II12cases、III20cases, IV26cases;17patients with lungcancer stage I and II were the early group,46patients with lung cancer stage III and stage IVwere advanced group. Detected contents of bFGF、MMP-9、TIMP-1in the two groups werebelonged to normal distribution using t-test, serum contents of TIMP-1、MMP-9、bFGF inpatients with advanced lung cancer were614.93+19.60pg/ml、609.17+6.14pg/ml、896.29+60.94pg/ml, serum contents of TIMP-1、MMP-9、bFGF in patients with early-stage lungcancer were566.69+19.70pg/ml、573.76+5.01pg/ml、562.64+13.84pg/ml. The serum contents of TIMP-1、MMP-9、bFGF in patients with advanced lung cancer was significantlyhigher than the serum contents of TIMP-1、MMP-9、bFGF in patients with early stage lungcancer,this result was statistically significant (P <0.05).②According to the differentiated degree,collection of lung cancer patients were dividedinto three groups, poorly differentiated group24cases, moderately differentiated group of15cases,24cases of well-differentiated group.Detected contents of bFGF、MMP-9、TIMP-1inthe three groups were belonged to normal distribution using t-test.The serum contents ofTIMP-1、MMP-9、bFGF in poorly differentiated group were607.32+19.73pg/ml、603.43+4.39pg/ml、941.92+9.16pg ml, the serum contents of TIMP-1、MMP-9、bFGF in poorlydifferentiated group were589.53+21.65pg/ml、589.53+21.65pg/ml、867.66+5.08pg/ml,theserum contents of TIMP-1、MMP-9、bFGF in poorly differentiated group were596.14+7.85pg/ml、564.14+18.95pg/ml、768.14+9.84pg/ml.The serum contents of TIMP-1、MMP-9、bFGF in poorly differentiated group were significantly higher than that the serum contents ofTIMP-1、MMP-9、bFGF in moderately differentiated group,the serum contents of TIMP-1、MMP-9、bFGF in moderately differentiated group were significantly higher than the serumcontents of TIMP-1、 MMP-9、 bFGF in well-differentiated group,those results werestatistically significant (P <0.05).③According to the distant metastasis degree,collection of lung cancer patientsweredivided into two groups,with distant metastasis26cases、without distant metastasis37cases. Detected contents of bFGF、MMP-9、TIMP-1in the two groups were belonged tonormal distribution using t-test.The serum contents of TIMP-1、MMP-9、bFGF in distantmetastasis group were600.62+19.54pg/ml、606.77+4.12pg/ml、996.28+6.84pg/ml,Theserum contents of TIMP-1、MMP-9、bFGF without distant metastasis groupwere578.70+18.71pg/ml、587.78+4.48pg/ml、846.21+7.28pg/ml. The serum contents of TIMP-1、MMP-9、bFGF indistant metastasis group were significantly higher than the serum contentsof TIMP-1、MMP-9、bFGF without distant metastasis group,this result was statisticallysignificant (P <0.05).④According to lymph node metastasis status,collection of lung cancer patientsweredivided into two groups, N1+N237cases, N326cases. Detected contents of bFGF、 MMP-9、TIMP-1in the two groups were belonged to normal distribution using t-test.Theserum contents of TIMP-1、MMP-9、bFGF in N3group were640.23+19.54pg/ml、592.12+3.61pg/ml、921.08+8.24pg/ml, The serum contents of TIMP-1、MMP-9、bFGF in N1+N2group were541.20+23.80pg/ml、588.21+5.44pg/ml、846.21+7.28pg/ml.The serum contentsof TIMP-1、MMP-9、bFGF inN3group were significantly higher than the serum contents ofTIMP-1、MMP-9、bFGF in N1+N2group,this result was statistically significant (P <0.05).⑤collection of lung cancer patients weredivided into three groups based on tumorsize,<3cm18cases、3-5cm25cases、>5cm20cases..Detected contents of bFGF、MMP-9、TIMP-1in the three groups were belonged to normal distribution using t-test.The serumcontents of TIMP-1、MMP-9、bFGF in>5cm group were618.78+4.65pg/m、615.33+23.21pg/ml、896.27+8.65pg/ml,The serum contents of TIMP-1、MMP-9、bFGF in3-5cm groupwere606.87+20.77pg/ml、597.36+8.39pg/ml、814.16+11.28pg/ml,The serum contents ofTIMP-1、MMP-9、bFGF in <3cm group were574.45+25.69pg/ml、592.11+3.59pg/ml、792.18+9.16pg/ml.The serum contents of TIMP-1、MMP-9、bFGF in>5cm group weresignificantly higher than the serum contents of TIMP-1、MMP-9、bFGF in3-5cm group,Theserum contents of TIMP-1、MMP-9、bFGF in3-5cm group weresignificantly higher than theserum contents of TIMP-1、MMP-9、bFGF in <3cm group,those results were statisticallysignificant (P <0.05).5、Found by Pearson correlation test,the serum contents of bFGF was significantcorrelation with MMP-9(r=0.807, P<0.01);the serum contents of MMP-9was significantlyrelated with TIMP-1(r=0.783, P <0.01), however,the serum contents of bFGF was notsignificantly related withTIMP-1(r=0.142, P <0.01).Conclusion:1、 The serum contents of basic fibroblast growth factor (bFGF)、 matrixmetalloproteinase-9(MMP-9)、matrix metalloproteinase to inhibit factor-1(TIMP-1) in lungcancer patients were significantly higher than serum contents of bFGF、MMP-9、TIMP-1inhealthy control group.Therefore,they were considered as lung cancer serum tumor markers forthe diagnosis in lung cancer.2、The serum contents of bFG、MMP-9、TIMP-1were not significant correlation the patients age, gender, smoking status in lung cancer patients and healthy control.3、The serum contents of bFG、MMP-9、TIMP-1was not significantly related withtumorpathological type in lung cancer.4、The serum contents of bFG、MMP-9、TIMP-1was closely related with TNM stage、distant metastasis、cell differentiation in lung cancer.The serum contents of TIMP-1、MMP-9、bFGF in patients with advanced lung cancer was significantly higher than the serum contentsof TIMP-1、MMP-9、bFGF in patients with early stage lung cancer; the serum contents ofTIMP-1、MMP-9、bFGF in distant metastasis group were significantly higher than the serumcontents of TIMP-1、MMP-9、bFGF without distant metastasis group;The serum contents ofTIMP-1、MMP-9、bFGF in poorly differentiated group were significantly higher than that theserum contents of TIMP-1、MMP-9、bFGF in moderately differentiated group,the serumcontents of TIMP-1、MMP-9、bFGF in moderately differentiated group were significantlyhigher than the serum contents of TIMP-1、MMP-9、bFGF in well-differentiated group,thoseresults were statistically significant.5、Found by Pearson correlation test,the serum contents of bFGF was significantcorrelation with MMP-9(r=0.807, P<0.01);the serum contents of MMP-9was significantlyrelated with TIMP-1(r=0.783, P <0.01),thence,TIMP-1、MMP-9、bFGF jointly involve intumor cell growth、apoptosis, and they were significantly related tumor invasion, this resultwas matched with mechanism that tumor multiple genes involved in pathogenesis.However,theserum contents of bFGF was not significantly related withTIMP-1(r=0.142, P <0.01),relationship of bFGF and TIMP-1gradually needs further exploration.
Keywords/Search Tags:Lung cancer, Enzyme linked immunosorbent assay(ELISA), tissueinhibitor of metalloproteinases-1(TIMP-1), matrix metalloproteinase-9(MMP-9), basicfibroblast growth factor(bFGF)
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