Zuo Qiangqiang, Zheng Weinan, Zhang Jinli, Pan Zemin, Liu Yinyin, Long Haichen, Fan Peiwen, Guo Caili, Li Feng, Shao Renfu
1 Department of Biochemistry, School of Medicine, Shihezi University, Xinjiang Endemic and Ethnic Disease and Education Ministry Key Laboratory, Shihezi, Xinjiang - PR China.
Int J Biol Markers. 2014 Dec 9;29(4):e354-62. doi: 10.5301/jbm.5000107.
We assessed the suitability of HS3ST2 and CCNA1 genes as biomarkers for the early detection of cervical cancer in Uygur women in Xinjiang, China. Methylation-specific PCR (MSP) and HPV (HPV16 and HPV18)-specific PCR were performed on 110 cervical samples: 40 normal cervices, 10 cervical intraepithelial neoplasia 1 (CIN1), 10 CIN2, 10 CIN3 and 40 cervical cancer tissues. The expression of the 2 genes was measured by reverse transcription PCR (RT-PCR) in 10 methylation-positive and 10 methylation-negative cervical tissues. We found that both HS3ST2 and CCNA1 genes were methylated in 38 of the 40 cervical cancer tissues, 9 of the 10 CIN3, and 6 of the 10 CIN2. In contrast, methylation of these 2 genes was found in only 1 of the 40 normal tissues and none of 10 CIN1. Furthermore, hypermethylated HS3ST2 and CCNA1 genes were correlated with infection with HPV16 and HPV18 in high-grade squamous intraepithelial lesions (HSILs) and cervical cancer (both p<0.05). The expression of HS3ST2 and CCNA1 genes was lower in the methylation-positive cervical tissues than in the methylation-negative cervical tissues. Our results indicate that HS3ST2 and CCNA1 genes may play important roles in HPV-induced cervical cancer and that patients with specific hypermethylated genes may have a greater risk of progressing to invasive cervical cancer.
我们评估了HS3ST2和CCNA1基因作为中国新疆维吾尔族女性宫颈癌早期检测生物标志物的适用性。对110份宫颈样本进行了甲基化特异性PCR(MSP)和HPV(HPV16和HPV18)特异性PCR检测:40份正常宫颈组织、10份宫颈上皮内瘤变1级(CIN1)、10份CIN2、10份CIN3以及40份宫颈癌组织。通过逆转录PCR(RT-PCR)检测了10份甲基化阳性和10份甲基化阴性宫颈组织中这两个基因的表达。我们发现,在40份宫颈癌组织中的38份、10份CIN3中的9份以及10份CIN2中的6份中,HS3ST2和CCNA1基因均发生了甲基化。相比之下,在40份正常组织中仅1份发现这两个基因甲基化,而10份CIN1中均未发现。此外,在高级别鳞状上皮内病变(HSILs)和宫颈癌中,HS3ST2和CCNA1基因的高甲基化与HPV16和HPV18感染相关(两者p<0.05)。甲基化阳性宫颈组织中HS3ST2和CCNA1基因的表达低于甲基化阴性宫颈组织。我们的结果表明,HS3ST2和CCNA1基因可能在HPV诱导的宫颈癌中发挥重要作用,特定基因发生高甲基化的患者进展为浸润性宫颈癌的风险可能更高。