Preserved SCN4B expression is an independent indicator of favorable recurrence-free survival in classical papillary thyroid cancer

Voltage-gated sodium channel beta subunits (encoded by SCN1B to SCN4B genes) have been demonstrated as important multifunctional signaling molecules modulating cellular processes such as cell adhesion and cell migration. In this study, we aimed to explore the expression profiles of SCN4B in papillary thyroid cancer (PTC) and its prognostic value in terms of recurrence-free survival (RFS) in classical PTC. In addition, we also examined the potential effect of DNA methylation on its expression. A retrospective study was performed by using data from available large databases, including the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA)-Thyroid Cancer (THCA). Results showed that SCN4B is downregulated at both RNA and protein level in PTC compared with normal thyroid tissues. Preserved SCN4B expression was an independent indicator of favorable RFS in patients with classical PTC, no matter as categorical variables (HR: 0.243, 95%CI: 0.107-0.551, p = 0.001) or as a continuous variable (HR: 0.684, 95%CI: 0.520-0.899, p = 0.007). The methylation status of one CpG site (Chr11: 118,022,316-318) in SCN4B DNA had a moderately negative correlation with SCN4B expression in all PTC cases (Pearson's r = -0.48) and in classical PTC cases (Pearson's r = -0.41). In comparison, SCN4B DNA copy number alterations (CNAs) were not frequent and might not influence its mRNA expression. In addition, no somatic mutation was found in SCN4B DNA. Based on these findings, we infer that preserved SCN4B expression might independently predict favorable RFS in classical PTC. Its expression might be suppressed by DNA hypermethylation, but is less likely to be influenced by DNA CNAs/mutations.