AUTHOR=Li Ang , Wu Hongjiao , Tian Qinqin , Zhang Yi , Zhang Zhi , Zhang Xuemei 

TITLE=Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.620200

DOI=10.3389/fonc.2021.620200

ISSN=2234-943X

ABSTRACT=<p>This study aims to analyze the methylation regulation of <italic>TLR3</italic> in lung adenocarcinoma (LUAD) and to explore the association of <italic>TLR3</italic> expression with immune microenvironment. <italic>TLR3</italic> has a decreased expression in LUAD tissues and low expression of <italic>TLR3</italic> 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 <italic>TLR3</italic> was negatively correlated with the level of <italic>TLR3</italic> mRNA in LUAD tissues. TIMER analysis showed that <italic>TLR3</italic> was negatively correlated with the tumor purity of LUAD and positively with immune cell infiltration to some extent. ESTIMATE analysis also suggested that <italic>TLR3</italic> 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 <italic>TLR3</italic> might inhibit the development of LUAD by activating apoptosis pathway. The proteins interacted with <italic>TLR3</italic> were mainly involved in the apoptosis pathway and positively correlated with the key genes (<italic>MYD88</italic>, <italic>Caspase 8</italic>, <italic>BIRC3</italic>, <italic>PIK3R1</italic>) in this pathway. Therefore, <italic>TLR3</italic> as a key biomarker for prognosis and diagnosis in LUAD, might be considered as a potential epigenetic and immunotherapeutic target.</p>