The Study Of Promoter Methylation Of IGFBP-rP1Gene And Its Protein Expression In LSCC

Objective: Carcinoma of larynx is one of the most common malignanttumors in the head and neck tumors. In resent years, the mortality of LSCC isstill increasing. As other maligament tumors, the LSCC is concerned withrelated genetic expression which caused by various factors.DNA methylation is active in present research, and it is the importantcontent of epigenetic mechanisms. In this study, we investigated the promotermethylation status of insulin-like factor binding protein-related protein1(IGFBP-rP1) and its protein expression in LSCC and corresponding normaltissues. We also investigated the protein expression of insulin-like growthfactor binding protein3(IGFBP-3), which is one member of the super-family.And we tried to explore its correlation with carcinogenesis, infiltration,metastasis and pathological differentiation of LSCC. Thus we focused on thestudy of epigenetic modulation of IGFBP-rP1expression in LSCC, to providea new theory and experimental evidence for pathogenesy, gene therapy andimmunotherapy, clinical prognosis of LSCC.Methods:1Methylation specific PCR (MSP) method was used to examine themethylation status of the promoter of IGFBP-rP1gene in45cases ofLSCC and18cases of corresponding normal tissues.2Immunohistochemistry method was used to examine the proteinexpression of IGFBP-rP1and IGFBP-3in LSCC tumor tissues andcorresponding normal tissues.3SPSS13.0was applied to analyze the results of experiment.Results:1The relationship between methylation status of IGFBP-rP1promoter and LSCC clinical pathology:Methylation frequency of IGFBP-rP1in tumor specimens (33.3%,15/45)was significantly higher than that in corresponding nomal tissues (5.6%,1/18)(P<0.05). Methylation status of IGFBP-rP1gene was not associated withTNM stage, differential degree, lymph node status, tumor size and age.(P>0.05).2IGFBP-rP1protein expression in tumor specimens and correspondingnormal tissues:The protein expression of IGFBP-rP1in tumor specimens (26.7%,12/45)was significantly lower than that in corresponding tissues (88.9%,16/18)(P<0.01). In tumor tisusses, protein expression of IGFBP-rP1was notcorrelated with age, differential degree, TNM stage and tumor size (P>0.05).However it was associated with lymph node metastasis(χ2=5.114, P=0.024),the protein expression of IGFBP-rP1in lymph node metastasis group (10.0%)was significantly lower than that in non lymph node metastasis group (40.0%)(P<0.05).The positive protein expression of IGFBP-rP1in methylated tumor tissues(0%,0/15) was significantly lower than that in unmethylated tumor tissues(40.0%,12/30)(P<0.05). IGFBP-rP1protein expression was inverselycorrelated with its promoter methylation status (P<0.05).3IGFBP-3protein expression in tumor specimens and correspondingnormal tissues:The protein expression of IGFBP-3in tumor specimens (24.4%,11/45) wassignificantly lower than that in corresponding tissues (72.2%,13/18)(P<0.01).In tumor tisusses, protein expression of IGFBP-3was not correlated with age,differential degree, TNM stage and tumor size (P>0.05). However it wasassociated with lymph node metastasis (χ2=5.595, P<0.05), the proteinexpression of IGFBP-3in lymph node metastasis group (5.0%) wassignificantly lower than that in non lymph node metastasis group (40.0%)(P<0.05).4There was a positive correlation between IGFBP-3protein and IGFBP-rP1 protein in laryngeal squamous cell carcinoma tissues (r=0.826, p<0.01).Conclusions:1Methylation of IGFBP-rP1in promoter may be one of the mechanisms thatlead to the occurrence of LSCC. However, it was not associatied age, the sizeof tumors, TNM stage and lymph node metastasis of patients, that suggestedthe promoter methylation status of IGFBP-rP1may be not associated with thedevelopment of LSCC.2There seemed to be a correlation between the low expression of IGFBP-rP1and LSCC, and hypermenthylation of IGFBP-rP1promoter may be one of thereasons that lead to down-expression of IGFBP-rP1in LSCC.3IGFBP-rP1and IGFBP-3maybe collectively participated in process ofLSCC and pathological progression of neoplasm metastasis.