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Functional Research On Oral Leukoplakia Carcinogenesis Of STATs Family

Posted on:2012-10-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:W W LiuFull Text:PDF
GTID:1114330368975459Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
The aim of this study was to identify genes that are predictive of carcinogenic change in patients of oral leukoplakia (OLK) using a cancer-related microarray. Candidate biomarkers were discovered using the Oligo GEArray OHS-802 and validated on independent samples by semi-quantitative reverse transcription-PCR (RT-PCR) and real-time RT-PCR. Both the discovery and the validation cohorts of samples included normal oral tissues, OLK tissues, and oral squamous cell carcinoma (OSCC) tissues. And then we used Western Blotting to detect the relationship between OLK carcinogenesis and the degree of STATs phosphorylation, and with the expression level of STATs in three kind of oral mucosa (normal oral tissue, OLK and OSCC). STAT3 is a very important transcription factor in JAK-STAT signal transduction pathway. What's the fuction of STAT3 in OLK carcinogenesis? Further, by using immunohistochemistry, we tried to decide the position of STAT3 in OLK and OSCC and the variation among the three kinds of oral mucosa.Based on the microarray results, we found that there were nine genes successively up-regulated or down-regulated more than two fold between the normal group and OLK group and then again between the OLK group and OSCC group. The expression level of the nine signature genes had statistically significant differences (p<0.05) between OLK and normal groups and between OSCC and OLK groups. In summary, the expression of the 9 signature genes might be representative of OLK carcinogenesis. A cancer-related microarray was used to identify a panel of candidate biomarkers for determining carcinogenesis of OLK lesions, in combination with semi-quantitative and real-time RT-PCR to validate the results. And there is a close correlation between the OLK carcinogenesis with the protein level of STATs and pSTATs in three different kinds of oral mucosa. The STAT3 always expressed in cytoplasm the oral mucosa cells, and the more it is expressed, the more serious of the oral mucosa tissue is.Our data indicated that alterations in gene expression that result in carcinogenesis can be identified in precancerous oral tissues.
Keywords/Search Tags:Genechip, Oral leukoplakia/OLK, Oral squamous carcinoma/OSCC, STATs, STAT3
PDF Full Text Request
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