Down-regulation of DLEC1 in sinonasal inverted papilloma and squamous cell carcinoma

• Main Authors: Po Hung Chang, 張伯宏
• Other Authors: C. N. Tsai
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/85941756919013112662

碩士 === 長庚大學 === 臨床醫學研究所 === 100 === Sinonasal inverted papilloma (IP) is known for a tendency to recur, invasion of surrounding tissues, and an association with squamous cell carcinoma (SCC). This study aimed to investigate differential gene expression profile using microarrays, dissect the role of the DLEC1 in the tumorigenesis and carcinogenesis of IP, and analyze if human papilloma virus (HPV) in the IP and SCC samples was associated with repression of DLEC1. In our prospective study, we analyzed differentially expressed transcripts of DLEC1 in SCC (n=5), IP (n=5) and normal mucosa (n=5) using microarrays and further validating by quantitative real-time polymerase(QRT-PCR) chain reaction. To further examine the mechanism, methylation-specific polymerase chain reactions and subsequent autosequencing were also used to examine the methylation status of DLEC1 promoter in the same samples as the microarray training set. To examine the expression of DLEC1 in a large validation set, it was evaluated by immunohistochemistry (n=25 in SCC, IP and normal mucosa). HPV subtypes were determined by nested PCR. DLEC1 was down-regulated in IP and SCC tissues compared to normal mucosa (p < 0.01 both in immunohistochemistry and QRT-PCR), with SCC more repressed (p < 0.01, p = 0.024, respectively in QRT-PCR and immunohistochemistry) than IP tissues. Repression of DLEC1 in SCC tissues was via promoter hypermethylation, which was not observed in IP tissues. No significant difference of DLEC1 expression was observed in HPV-positive and HPV-negative IP and SCC tissues. In conclusion, In sinonasal SCC and IP, DLEC1 was down-regulated but exhibited a distinct mechanism. Inactivation of DLEC1 in SCC occurred through DNA methylation, whereas this mechanism was not observed in IP. HPV infection was not observed to have a role in the repression of DLEC1.