CpG islands in MyD88 and ASC/PYCARD/TMS1 promoter regions are differentially methylated in head and neck squamous cell carcinoma and primary lung squamous cell carcinoma

Diagnostic Pathology

Miroslav Samaržija¹  Marko Jakopović¹  Mario Bilić²  Lana Kovač Bilić²  Antonija Jakovčević³  Sven Seiwerth³  Luka Brčić⁴  Jurica Baranašić⁵  Maja Šutić⁵  Jelena Knežević⁶  Ulrich Zechner⁷ 

[1] Department for Respiratory Diseases, Clinic for Respiratory Diseases Jordanovac, University of Zagreb, School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia;Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia;Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia;Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria;Division of Molecular Medicine, Laboratory for Advanced Genomics, Ruđer Bošković Institute, Zagreb, Croatia;Division of Molecular Medicine, Laboratory for Advanced Genomics, Ruđer Bošković Institute, Zagreb, Croatia;Faculty for Dental Medicine and Health, University of Osijek, Osijek, Croatia;Institute for Human Genetics, Johannes Gutenberg-University Mainz, Mainz, Germany;

关键词: HNSCC;    Second primary tumor;    Lung;    Diagnostic biomarker;    Methylation;    CpG;   

DOI  :  10.1186/s13000-021-01078-3

来源: Springer

【 摘 要 】

BackgroundPatients with head and neck squamous cell carcinoma (HNSCC) can develop lung squamous cell carcinoma (LuSCC), which could be the second primary tumor or HNSCC metastasis. Morphologically it is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs.MethodsPrimary HNSCC (N = 36) and LuSCC (N = 17) were included in this study. Methylation status in the ASC/TMS1/PYCARD (apoptosis-associated speck-like protein containing a caspase recruitment domain; 8 CpG sites) and MyD88 (Myeloid differentiation primary response protein 88; 10 CpG sites) promoters was analyzed. Bisulfite converted DNA, isolated from tumor tissue was quantified using pyrosequencing. Results of pyrosequencing analysis were expressed as a percentage for each tested CpG site. Receiver-operating characteristic (ROC) curve analysis was used for the evaluation of the diagnostic properties of selected biomarkers.ResultsCpG sites located in the promoters of ASC/TMS1/PYCARD_CpG8 (− 65 upstream) and MyD88_CpG4 (− 278 upstream) are significantly hypermethylated in the HNSCC when compared with LuSCC (p ≤ 0.0001). By performing ROC curve analysis we showed that corresponding areas under the curve (AUC) were 85–95%, indicating that selected CpG sites are useful for a distinction between primary LuSCC and primary HNSCC.ConclusionsResults of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and LuSCC. However, to prove this approach as a useful tool for distinguishing second primary LuSCC from HNSCC metastasis, it would be necessary to include a larger number of samples, and most importantly, metastatic samples.

【 授权许可】

CC BY