Putative biomarkers of malignant transformation of sinonasal inverted papilloma into squamous cell carcinoma
Putative biomarkers of malignant transformation of sinonasal inverted papilloma into squamous cell carcinoma
复制标题
鼻窦内翻性乳头状瘤恶性转化为鳞状细胞癌的假定生物标志物
DOI：
10.1177/0300060519838385
复制
发表时间：
2019-06-01
影响因子：
1.6
通讯作者：
Zhang, Luo
中科院分区：
文献类型：
--
作者：
Yang, Zheng;Zhang, Yang;Zhang, Luo
目的比较鼻腔鼻窦内翻性乳头状瘤（SNIP）和鳞状细胞癌（SCC）的全基因组DNA甲基化水平，寻找可能参与恶性转化的异常甲基化基因。方法收集患者的组织标本。使用DNA甲基化微阵列试剂盒分析C-磷酸-G岛和基因启动子中的DNA甲基化。使用实时聚合酶链反应或蛋白质印迹分析测量异常甲基化基因的mRNA或蛋白质水平。结果共27例组织标本纳入本研究，其中15例为SNIP标本，12例为SNIP引起的SCC。在SNIP和SCC之间共观察到11201个名义上的差异甲基化位点。有6个位点差异显著（P < 0.01），包含3个基因（MIR 661、PLEC和OPA 3）。这三个基因是高甲基化的。此外，与SNIP样本相比，SCC组织中成熟miR-661 mRNA和PLEC蛋白的水平显著上调。OPA 3蛋白在SCC组织中的表达水平较SNIP组明显下调。结论MIR 661、PLEC和OPA 3基因在SNIP中存在高甲基化和异常表达，可能参与SNIP的恶性转化。
Objective To compare genome-wide DNA methylation between samples of sinonasal inverted papilloma (SNIP) and squamous cell carcinoma (SCC) samples in order to identify aberrantly methylated genes that might be involved in malignant transformation. Methods Tissue samples were collected from patients. DNA methylation in C-phosphate-G islands and gene promoters was analysed using a DNA methylation microarray kit. The levels of mRNA or protein from aberrantly methylated genes were measured using real-time polymerase chain reaction or Western blot analysis. Results A total of 27 tissue samples were included in this study; 15 SNIP samples and 12 SCCs arising in SNIPs. A total of 11 201 nominally differentially methylated sites were observed between SNIP and SCC arising in SNIPs. Six sites were significantly different at P < 0.01 and contained three genes (MIR661, PLEC and OPA3). These three genes were hypermethylated. In addition, the levels of mature miR-661 mRNA and PLEC protein were significantly upregulated in SCC tissues compared with SNIP samples. The levels of OPA3 protein were downregulated in SCC tissues compared with SNIP samples. Conclusions This study demonstrated hypermethylation and abnormal expression of the MIR661, PLEC and OPA3 genes, suggesting a role for their involvement in the malignant transformation of SNIP.