JAK3 and TYK2 Serve as Prognostic Biomarkers and Are Associated with Immune Infiltration in Stomach Adenocarcinoma

Abstract

Background. Stomach adenocarcinoma (STAD) is one of the most common malignant tumors. The Janus kinases (JAKs) play a significant part in cellular biological process, inflammation, and immunity. The roles of JAKs in STAD are still not systematically described. Methods. A series of bioinformatics tools were used to clarify the role of JAKs in STAD. Results. JAK3/TYK2 levels were significantly increased in STAD during subgroup analyses based on gender, tumor grade, cancer stages, and nodal metastasis status. STAD patients with high levels of JAK3/TYK2 had poor overall survival, postprogression survival, and first progression. Immune infiltration revealed a significant correlation between JAK3/TYK2 expression and the abundance of immune cells as well as immune biomarker expression in STAD. JAK3/TYK2 was associated with the adaptive immune response, chemokine signaling pathway, and JAK-STAT signaling pathway. Conclusions. JAK3 and TYK2 serve as prognostic biomarkers and are associated with immune infiltration in STAD.

Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma

“…This analysis provides preliminary data on the role of ARID1A in CTL infiltration. To learn more about the effects of ARID1A on immunological infiltration, we evaluated previously described biomarkers of major immune cell types ( 15 , 26 ) and their association with ARID1A levels ( Table 1 ). Reportedly, the immunoinhibitory molecules attach to the PD-1 receptor on the surface of CD8+ T cells to stop their function.…”

“…Reportedly, the immunoinhibitory molecules attach to the PD-1 receptor on the surface of CD8+ T cells to stop their function. Hence these molecules view immunotherapy resistance as the primary cause ( 15 ). While ARID1A deficiency enhanced PDL-1 expression ( 24 ), the findings of this study generally validated prior research in this field and proved that ARID1A deletion may influence immunity-related pathways.…”

TYK2 in Cancer Metastases: Genomic and Proteomic Discovery

“…Proteomic phosphotyrosine peptide enrichment and quantitative mass spectrometry identified several activated kinases, including TYK2 (Y 292 ) and its downstream target signal transducer and activator of transcription 3 (STAT3) (Y 705 ), in metastatic castration-resistant prostate cancer [13]. In addition, RNA sequencing (RNA-seq) of the transcriptome revealed that TYK2 and JAK3 mRNA levels were significantly increased in stomach adenocarcinoma, and both proteins were found to be prognostic biomarkers [14]. Genomic screens have also implicated TYK2 as a pro-survival gene in soft-tissue sarcomas (Table 1).…”

“…Epithelial-to-mesenchymal transition (EMT) is a pre-programmed process by which polarized epithelial cancer cells de-differentiate into stem cells that can migrate and invade, [18,20,41,106,108,109] while stimulating proliferation [20,41,106,108,113], migration, invasion [113][114][115][116][117][118], and resistance to chemotherapy [107]. These functions of TYK2 lead to increased tumor aggressiveness and metastasis [14,20,22,36,106], resulting in greater patient mortality. Arrows (↑ or ↓) indicate direction of gene expression or protein activation change.…”

“…Epithelial-to-mesenchymal transition (EMT) is a pre-programmed process by which polarized epithelial cancer cells de-differentiate into stem cells that can migrate and invade, allowing the cells to metastasize to other locations in the body [124,125]. In a series of recent genomic, proteomic, cell-based and mouse model studies, TYK2 has emerged as an oncogene that promotes migration, invasion and metastasis in multiple types of cancer, including stomach, MPNST, breast cancer, liver cancer, colon cancer, prostate cancer and lung cancer [14,20,22,[114][115][116].…”