IL22RA1/JAK/STAT Signaling Acts As a Cancer Target Through Pan-Cancer Analysis

Abstract

Cytokines and cytokine receptors are important mediators in immunity and cancer development. Interleukin 22 (IL22) is one of the most important cytokines which has protumor effect. Given that common and specific roles of cytokines/receptors in multiple cancers, we conducted a pan-cancer study to investigate the role of IL22RA1 in cancer using The Cancer Genome Atlas (TCGA) database. Notably, we found IL22RA1 transcript was upregulated in 11 cancer types compared with their corresponding control. The mRNA expression level of IL22RA1 was highest in the pancreas among tumor tissues. The higher expression of IL22RA1 was associated with worse overall survival rate in patients. A total of 30 IL22RA1-correlated genes (e.g. IL17D, IL22RA2, IL20RB, IL10RA, IL10RB, TSLP and TYK2) are involved in the JAK/STAT pathway which promotes tumor progression. The upregulation of IL22RA1 in tumors was correlated with immune cell infiltration level. Higher expression of IL22RA2, IL20RB, IL10RA, IL10RB, TSLP, TYK2, STAT1 and STAT3 was associated with decreased overall survival rate in patients. IL22RA1 mutation was observed more in uterine cancer and melanoma compared with the other cancer types. Deactivation of IL22RA1 induced a lot of changes in gene expression. IL22RA1 mutants had upregulated DNA damage/repair genes in uterine cancer, whereas downregulated genes in the FoxO signaling pathway. In melanoma, mutation of IL22RA1 can upregulate the HIF signaling pathway but downregulate metabolic pathways. Our study suggests that IL22RA1/JAK/STAT signaling can be an important target for cancer treatment.

Depleted-MLH1 Expression Predicts Prognosis and Immunotherapeutic Efficacy in Uterine Corpus Endometrial Cancer: An In Silico Approach

“…The increased expression of IL10RB was found to be associated with a poorer overall survival rate in UCEC. This could be attributed to the activation of the JAK/STAT pathway, which facilitates tumor progression [55]. The mRNA expression of CXCL12 was significantly lower in UCEC samples [56].…”

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…The JAK/STAT signaling pathway, a critical mediator in various cellular functions, has emerged as a significant player in the progression of cancer, including UM, where its aberrant activation has been linked to increased growth, survival, and malignancy of tumor cells [ 9 , 10 ]. In UM GEPs, the HTR2B (5-hydroxytryptamine receptor 2B) stands out as the most dysregulated mRNA transcript in high-risk MUMs and has connections with the JAK/STAT pathway.…”

“…These molecular discoveries have led to the subclassification of UMs which, in turn, has significant prognostic implications and has become integral to patient management, guiding therapeutic decisions and enabling personalized treatment approaches (reviewed in [ 8 ]). Signaling pathways play a pivotal role in tumorigenesis and progression in many cancers, such as the JAK/STAT, mTOR and β-catenin pathways, among others (reviewed in [ 9 , 10 , 11 , 12 , 13 ]). Understanding these pathways and the broader immune microenvironment offers new targets for therapeutic interventions [ 14 ].…”

Inflammation and Neurodegeneration in Glaucoma: Isolated Eye Disease or a Part of a Systemic Disorder? - Serum Proteomic Analysis

“…Zhang et al identified 11 types of cancer associated with upregulated transcript levels of IL22RA1. 84 The authors noted that patients' poor survival was linked to greater gene expression. IL22RA1 polymorphisms were also linked with chronic rhinosinusitis occurrence and severity.…”