Putative biomarkers of malignant transformation of sinonasal inverted papilloma into squamous cell carcinoma
Zheng Yang 1 2 , Yang Zhang 1 2 , Xiangdong Wang 1 2 , Junwei Huang 1 2 , Wei Guo 1 2 , Peng Wei 3 , Guojun Li 4 5 , Ziqiao Wang 3 , Zhigang Huang 1 2 , Luo Zhang 1 2
- 1 1 Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
- 2 2 Key Laboratory of Otolaryngology Head and Neck Surgery of the Ministry of Education, Beijing, China.
- 3 3 Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 4 4 Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 5 5 Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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.
Keywords: C-phosphate-G islands; Sinonasal inverted papilloma; epigenetics; methylation; squamous cell carcinoma.