Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was...Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was to investigate the association of cervical cancer development with the RARβ gene expression at the mRNA and protein level to assess the impact of RARβ as a marker for early detection of the cancer.Methods:We collected 126 cases of formalin fixed and paraffin embedded cervical tissue specimens as well as 37 cases of fresh tissue samples from women with cervicitis,cervical intraepithelial neoplasia(CIN) and cervical squamous cell carcinoma(CSCC).The RARβ mRNA and protein expression was detected by quantitative RT-PCR and immunohistochemistry,respectively.Results:(1) The mRNA expression of RARβ in CIN and cervical cancer was markedly decreased compared to cervicitis with a statistically very significant difference,but no difference was found between CIN and cervical cancer.(2) RARβ protein was normally expressed in the epithelial cells of cervicitis and partially lost in a few cases,but with the development of cervical lesion pathogenesis and cancer,a significant loss of protein expression was detected in CIN(38%) and CSCC(57%) compared to cervicitis(P < 0.01).Conclusion:The downregulation of RARβ transcription or loss of protein expression is an important indicator of cervical cancer and its precursur lesions.The detection of RARβ expression coupled with aberrant methylation of the gene may become a biomarker for the early prognosis or diagnosis of the cancer.展开更多
基金Supported by a grant from the Natural Science Foundation of China (No. 30760279)
文摘Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was to investigate the association of cervical cancer development with the RARβ gene expression at the mRNA and protein level to assess the impact of RARβ as a marker for early detection of the cancer.Methods:We collected 126 cases of formalin fixed and paraffin embedded cervical tissue specimens as well as 37 cases of fresh tissue samples from women with cervicitis,cervical intraepithelial neoplasia(CIN) and cervical squamous cell carcinoma(CSCC).The RARβ mRNA and protein expression was detected by quantitative RT-PCR and immunohistochemistry,respectively.Results:(1) The mRNA expression of RARβ in CIN and cervical cancer was markedly decreased compared to cervicitis with a statistically very significant difference,but no difference was found between CIN and cervical cancer.(2) RARβ protein was normally expressed in the epithelial cells of cervicitis and partially lost in a few cases,but with the development of cervical lesion pathogenesis and cancer,a significant loss of protein expression was detected in CIN(38%) and CSCC(57%) compared to cervicitis(P < 0.01).Conclusion:The downregulation of RARβ transcription or loss of protein expression is an important indicator of cervical cancer and its precursur lesions.The detection of RARβ expression coupled with aberrant methylation of the gene may become a biomarker for the early prognosis or diagnosis of the cancer.