Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Department of Emergency, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Asia Pac J Clin Oncol. 2022 Apr;18(2):e129-e140. doi: 10.1111/ajco.13569. Epub 2021 Apr 14.
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.
肺腺癌（LUAD）仍然是一种发病率和死亡率都很高的主要疾病。Janus 激酶（JAKs）在细胞生物学过程、炎症和免疫中起着重要作用。JAK 家族在 LUAD 中的作用仍不清楚。
应用各种生物信息学网络门户探讨 JAK 家族在 LUAD 中的预后价值及其与免疫浸润的相关性。
与健康对照组相比，在基于性别、年龄、吸烟习惯、癌症分期、TP53 突变状态和淋巴结转移状态的亚组分析中，LUAD 患者的 JAK1/2 下调，而 JAK3/TYK2 上调。药物敏感性表明 JAK3 和 TYK2 表达低对大多数小分子或药物有耐药性。高 TYK2 表达与 LUAD 的总生存和无复发生存良好相关。此外，单因素和多因素分析显示，临床分期、淋巴结转移和 TYK2 表达是影响 LUAD 患者预后的独立因素。LUAD 患者 TYK2 表达与免疫细胞（B 细胞、CD8+T 细胞、CD4+T 细胞、中性粒细胞和树突状细胞）和免疫生物标志物集的丰度呈正相关。此外，TYK2 主要参与 RNA 结合、癌症转录失调和细胞周期。我们还在 LUAD 中鉴定了几种与 TYK2 相关的 miRNA 或转录因子靶标。
我们的结果表明，TYK2 是 LUAD 的一个标志物，与预后和免疫浸润有关，为进一步研究 TYK2 在 LUAD 的发生和发展中的作用奠定了基础。
