The differential gene expression of Osteopontin in oral carcinogenesis and the primary exploration of the role of single nucleotide polymorphisms at Osteopontin gene promoter

碩士 === 國立陽明大學 === 臨床牙醫學研究所 === 96 === Background: Osteopontin (OPN) is a highly phosphorylated and glycosylated protein in the extracellular matrix of bone, cementum, and cartilage, and it plays multifaceted roles in regulating bone remodeling and tumorigenesis/metastasis in breast, prostate, lung,...

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Bibliographic Details
Main Authors: Yu-Wei Chiu, 邱昱瑋
Other Authors: Shou-Yen Kao
Format: Others
Language:zh-TW
Published: 2008
Online Access:http://ndltd.ncl.edu.tw/handle/58879868294760514575
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Summary:碩士 === 國立陽明大學 === 臨床牙醫學研究所 === 96 === Background: Osteopontin (OPN) is a highly phosphorylated and glycosylated protein in the extracellular matrix of bone, cementum, and cartilage, and it plays multifaceted roles in regulating bone remodeling and tumorigenesis/metastasis in breast, prostate, lung, colon, and esophageal SCC (squamous cell carcinoma). The expression of OPN also relates to its polymorphism at promoter area (-66, -156, -443). Purpose: This study is to detect whether the expression of OPN is related to oral carcinogenesis and to explore the promoter polymorphisms (-66T/G, -156G/GG, -443T/C) and the risk for the development of OSCC (oral squamous cell carcinoma). Materials and methods: IHC was used to detect the expression of OPN from adjacent normal and cancer tissues in 68 OSCC cases. DNA isolated from blood of 97 OSCC cases and 100 normal controls was amplified by PCR and sequenced for the single nucleotide polymorphism (SNP) in promoter (626 nucleotides) area. Clinical covariates relating to expression and its SNP were analyzed via Fisher’s exact test. Result: The expression of OPN was significantly high in OSCC than its adjacent normal tissue (p<0.001), and the expression of OPN was significantly correlates to the lymph node metastasis (p<0.05) and advanced stages IV (p<0.05). A significantly higher percentage of genotype GG/GG at –156 and genotype T/T at -443 promoter site in OSCC (18/97, 18.5%) (47/97 48.4%) than in normal (9/100, 9%) (33/100, 33%) (odds ratio 3.11 p<0.05) (odds ratio 2.6 p<0.05). Also, statistically significant difference was observed in haplotypes -443T/-156GG/-66T and -443C/-156G/-66T between OSCC cases (43.4% and 29.1%) and normal controls (32.1% and 40.6%) (odds ratio 1.86 p<0.05). The OPN immunoreactivity was significantly correlated with genotypes of G/G+G/GG and GG/GG groups (p<0.05). Conclusion: The results suggest that OPN expression indeed plays a role in oral carcinogenesis and OPN gene promoter -156G/G > GG/GG polymorphism was associated with OSCC risk. The OSCC patients with genotype GG/GG showed more OPN expression.