Hyperexpression and Hypomethylation of TM4SF1 Are Associated With Lymph Node Metastases in Papillary Thyroid Carcinoma Patients

Abstract Background: Lymph node metastases(LNM) is an indicator for recurrence in papillary thyroid carcinoma(PTC) patients.However,prophylactic neck dissection(ND) can not improve neither survival nor recurrence rate because of increased surgical complications and occult lymph node metastases.Biomarkers are needed for prediction of high-risk of LNM to avoid unnecessary operation and reduce the missed malignant lymph nodules.Methods: GEO database was searched for the differentially expressed genes (DEGs) between PTC patients with LNM(N1) and those without LNM(N0),transcriptional and methylation data of DEGs in THCA were examined from databases.The expression and methylation of TM4SF1 in fresh and paraffin tissues of PTC paitents were examined by qRT-PCR、IHC and MSP.Results: TM4SF1 was the only one significantly associated with LNM.Ualcan revealed that TM4SF1 was overexpression and hypomethylation in LNM patients.MEXPRESS presented a negative correlation between gene expression and promoter methylation of TM4SF1.DEGs were enriched to multiple pathways and Extracellular Matrix(ECM)-receptor interaction ptahway showed the greatest correlation with LNM.IHC and qRT-PCR of tissues demonstrated that the expression of TM4SF1 in N1 group were 4.5-fold higher than that in N0 group (P<0.05).MSP exhibited that the the positive rate of aberrant promoter methylation of TM4SF1 were 8.38% in N1 and 66.7% in N0 group(P<0.05).Conclusions: Hyperexpression and hypomethylation of TM4SF1 are associated with lymph node metastases in PTC patients.