TYK2 is a prognostic biomarker and associated with immune infiltration in the lung adenocarcinoma microenvironment

Abstract

Lung adenocarcinoma (LUAD) remains a major disease with high morbidity and mortality. The Janus kinases (JAKs) play a significant part in cellular biological process, inflammation and immunity. The role of JAK family in LUAD is still ambiguous. Various bioinformatics web portals were applied to explore the prognostic value of JAK family and their correlation with immune infiltration in LUAD. JAK1/2 was downregulated, whereas JAK3/TYK2 was upregulated in patients with LUAD compared with the healthy controls in subgroup analyses based on gender, age, smoking habits, cancer stage, TP53 mutation status, and nodal metastasis status. Drug sensitivity indicated that low expression of JAK3 and TYK2 were resistant to most of the small molecules or drugs. High TYK2 expression was associated with favorable overall survival and relapse free survival in LUAD. Moreover, univariate and multivariate analysis revealed that clinical stage, lymphatic node metastasis and TYK2 expression were the independent factors affecting the prognosis of LUAD patients. TYK2 expression in LUAD patients was positively associated with the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells) and immune biomarker sets. Moreover, TYK2 was mainly involved in RNA binding, transcriptional mis-regulation in cancer and cell cycles. We also identified several TYK2-associated miRNA or transcription factor targets in LUAD. Our results indicated that TYK2 was a biomarker and associated with prognosis and immune infiltration in LUAD, laying a foundation for further study about the role of TYK2 in the carcinogenesis and progression of LUAD.