Expression And Methylation Of TFPI-2in Human Non-Small-Cell Lung Carcinoma And The Correlation With Invasion And Metastasis Of Neoplasms

Objective：We observe the expression of TFPI-2in non-small-cell lung carcinoma andadjacent normal lung cancer tissue, and analysis the correlation between promoterhypermethylation and expression of TFPI-2, investigate the possible mechanism ofTFPI-2expression suppression as well as the relationship with invasion andmetastasis of NSCLC, which provide clues for NSCLC diagnosis and prognosisevaluation, to explore the new target for gene therapy of NSCLC.Methods：We collected the same NSCLC patients with lung cancer and adjacent normallung tissue specimens(defined as the edge of cancer>3cm)from the surgicalresection of the first affiliated hospital of NanChang university from2010to2011,the total example is30, sorting each specimen of clinical pathology material. TFPI-2mRNA and protein were measured using RT-PCR and immunohistochemistryrespectively in lung cancer and adjacent normal lung tissue, Methylation status of theTFPI-2gene promoter was detected by methylation specific PCR(MSP), which allhave the relevant analysis with clinical pathological significance.Results:1. Expression of TFPI-2in NSCLC: The positive rates of expression of TFPI-2mRNA in30cases of NSCLC and adjancent normal lung tissue were73.3%and96.7%respectively, there was a significant difference between the two groups(χ~2=4.706,P=0.030). The relative expression of TFPI-2mRNA in NSCLC tissue(0.405±0.219)was also significantly lower than the adjacent normal lung tissue(0.636±0.131), the difference was statistically significant (t=4.955,P=0.000).While the positive rates of protein expression were43.3%and86.7%respectively(χ~2=12.381,P=0.000).2. Hypermethylation of TFPI-2gene promoter and relationship with itsexpression: In30cases of NSCLC,10cases specimens were hypermethylation, there was only one case methylated in adjacent normal lung tissue, the positive rates ofhypermethylation were33.3%and3.3%, the difference was statistically significant(χ~2=9.017, P=0.003).There was correlation between hypermethylation andexpression of mRNA and protein of TFPI-2in NSCLN(P=0.007å'Œ0.017),Correlation coefficient were-0.533and-0.476respectively, they were moderatenegative correlation(P＜0.05), that was the expression of TFPI-2in positive group ofgene promoter hypermethylation less than negative groups.3. Correlation between expression and hypermethylation of TFPI-2and clinicalpathological significances: There was no correlation between expression andhypermethylation of TFPI-2and age,sex,smoking,Pathological type,differentiationdegree(P＞0.05), it was close related to lymph node metastasis and TNM stage(P＜0.05), With lymph node metastasis and TNM stage rising, expression of TFPI-2was falling subsequently, but the positive rates of hypermethylation was increasing.Concolusion:TFPI-2gene was lower expression in NSCLC, it was close correlation betweenhypermethylation of TFPI-2gene promoter CpG island and downregulation andsilence of TFPI-2expression, in addition, with lymph node metastasis and TNM stagerising, expression of TFPI-2was falling subsequently. TFPI-2maybe plays animportant role in invasion and metastasis of NSCLC, which become a new potentialsuppressor genes for providing basis in NSCLC diagnosis and prognosis evaluationand offering new targets in gene therapy of NSCLC.