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This study aims to analyze the methylation regulation of  TLR3  in lung adenocarcinoma (LUAD) and to explore the association of  TLR3  expression with immune microenvironment.  TLR3  has a decreased expression in LUAD tissues and low expression of  TLR3  is not only associated with poor prognosis in patients with LUAD, but also can be used as a diagnostic marker. Bisulfite sequencing PCR (BSP) results showed that the methylation level in the promoter of  TLR3  was negatively correlated with the level of  TLR3  mRNA in LUAD tissues. TIMER analysis showed that  TLR3  was negatively correlated with the tumor purity of LUAD and positively with immune cell infiltration to some extent. ESTIMATE analysis also suggested that  TLR3  expression and its methylation had significant correlation with immune score. The lower immune scores were associated with the late stage of LUAD and poor prognosis. The high expression of  TLR3  might inhibit the development of LUAD by activating apoptosis pathway. The proteins interacted with  TLR3  were mainly involved in the apoptosis pathway and positively correlated with the key genes ( MYD88 ,  Caspase 8 ,  BIRC3 ,  PIK3R1 ) in this pathway. Therefore,  TLR3  as a key biomarker for prognosis and diagnosis in LUAD, might be considered as a potential epigenetic and immunotherapeutic target.

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma