4.3 Article

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

期刊

DIAGNOSTIC PATHOLOGY
卷 16, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s13000-021-01078-3

关键词

HNSCC; Second primary tumor; Lung; Diagnostic biomarker; Methylation; CpG

资金

  1. Croatian Scientific Foundation [HrZZ-IP-2016-06-1441]

向作者/读者索取更多资源

The methylation status of genes in primary HNSCC and LuSCC significantly differs, with hypermethylation in specific CpG sites in HNSCC compared to LuSCC. ROC curve analysis demonstrates that these selected CpG sites are useful for distinguishing between primary LuSCC and primary HNSCC, with AUC values of 85-95%. Further studies with a larger sample size, particularly including metastatic samples, are needed to validate the usefulness of this approach in distinguishing second primary LuSCC from HNSCC metastasis.
Background Patients 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. Methods Primary 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. Results CpG 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. Conclusions Results 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.3
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据