High Expression of Interleukin-2 Receptor Subunit Gamma Reveals Poor Prognosis in Human Gastric Cancer

Wang, Deping; Zhao, Rong; Qi, Yuehong; Shen, Jing; Hou, Jiayi; Wang, Mei-Yue; Bi, Xiaogang; Guo, Xiaoqing; Cao, Ji‐Min

doi:10.1155/2021/6670834

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…As one of the most common tumors with a high morbidity and mortality, gastric cancer (GC) leads to a poor prognosis and increases critical social burden with 5.7% incidence and 8.2% mortality rates ( Bray et al, 2018 ). More than 50% of diagnosed GC patients were at advanced stages and the prognosis of GC was relatively poor with only less than 30% overall 5-year survival rate ( Yang et al, 2020a ; Wang et al, 2021 ). Despite remarkable progress have been made for the treatment of GC, including radiotherapy, chemotherapy and surgery according to different locations and clinical stages, there is still lack of effective strategies for the advanced GC treatment ( Ai and Wang, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

Pan

Jiang

et al. 2022

Front. Genet.

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Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

Pan

Jiang

et al. 2022

Front. Genet.

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“…A separate investigation disclosed the upregulation of IL-2RG in gastric cancer (GC) tissues, with high IL-2RG levels predicting a poorer OS. This suggests that IL-2RG may indeed have a role in developing human GC [ 21 , 22 ]. These collective findings, consistent with our results, reinforce the significance of IL-2RG in cancer biology.…”

Section: Discussionmentioning

confidence: 99%

“…IL-2RG influences malignant cell differentiation, activation, and proliferation, shaping the TME [ 20 ]. Particularly, IL-2RG expression has been identified in human gastric carcinomas and is associated with an unfavorable prognosis [ 21 , 22 ]. In recent years, the study of miRNAs in cancer research has gained significant attention due to their involvement in various biological processes, including carcinogenesis [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p

Gharib,

Rejali,

Piroozkhah

et al. 2024

J Transl Med

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Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays a pivotal role as a common subunit receptor in the IL-2 family cytokines and activates the JAK-STAT pathway. This study delves into the role of Interleukin-2 receptor gamma (IL-2RG) within the tumor microenvironment and investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming to discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed a significant upregulation of IL-2RG mRNA in TCGA-COAD samples and showed strong correlations with the infiltration of various lymphocytes. Single-cell analysis corroborated these findings, highlighting IL-2RG expression in critical immune cell subsets. To explore miRNA involvement in IL-2RG dysregulation, mRNA was isolated from the tumor tissues and lymphocytes of 258 CRC patients and 30 healthy controls, and IL-2RG was cloned into the pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney cell lines (HEK-293T) were transfected with this construct. Our research involved a comprehensive analysis of miRPathDB, miRWalk, and Targetscan databases to identify the miRNAs associated with the 3′ UTR of human IL-2RG. The human microRNA (miRNA) molecules, hsa-miR-7-5p and hsa-miR-26b-5p, have been identified as potent suppressors of IL-2RG expression in CRC patients. Specifically, the downregulation of hsa-miR-7-5p and hsa-miR-26b-5p has been shown to result in the upregulation of IL-2RG mRNA expression in these patients. Prognostic evaluation of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p, using TCGA-COAD data and patient samples, established that higher IL-2RG expression and lower expression of both miRNAs were associated with poorer outcomes. Additionally, this study identified several long non-coding RNAs (LncRNAs), such as ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, and MALAT1, which may act as competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-7-5p and hsa-miR-26b-5p. In summary, this investigation underscores the potential utility of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p as serum and tissue biomarkers for predicting CRC patient prognosis while also offering promise as targets for immunotherapy in CRC management. Graphical Abstract

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“…Jia et al [ 28 ] reported that CA19-9 and CEA may also be used as predictors of efficacy and progression-free survival for the CET + FOLFOX4 regimen in patients with advanced colorectal cancer. Moreover, changes in the inflammatory microenvironment are strongly linked to tumorigenesis and progression, of which pro-inflammatory IL-2 may be related to GC progression and poor prognosis, whereas the deficiency of anti-inflammatory factor IL-10 may be related to Helicobacter pylori infection + chronic alcohol-induced GC[ 29 , 30 ]. This study measured inflammation markers, IL-2 and IL-10.…”

Section: Discussionmentioning

confidence: 99%

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

Ying,

Huang,

Jing

et al. 2024

World J Clin Cases

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BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma (aGC), it may lead to an adverse prognosis. Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients. AIM To determine the efficacy and safety of cetuximab (CET) combined with the FOLFOX4 regimen (infusional fluorouracil, folinic acid, and oxaliplatin) as first-line therapy for patients with aGC, who received evidence-based care (EBC). METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled. Of these, 60 in the research group (RG) received CET + FOLFOX4 as first-line therapy, whereas 57 in the control group (CG) received FOLFOX4. The efficacy [clinical response rate (RR) and disease control rate (DCR)], safety (liver and kidney dysfunction, leukopenia, thrombocytopenia, rash, and diarrhea), serum tumor marker expression [STMs; carbohydrate antigen (CA) 19-9, CA72-4, and carcinoembryonic antigen (CEA)], inflammatory indicators [interleukin (IL)-2 and IL-10], and quality of life (QOL) of the two groups were compared. RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG, with an equivalent safety profile between the two groups. RG exhibited notably reduced CA19-9, CA72-4, CEA, and IL-2 levels following treatment, which were lower than the pre-treatment levels and those in the CG. Post-treatment IL-10 was statistically increased in RG, higher than the pre-treatment level and the CG. Moreover, a significantly improved QOL was evident in the RG. CONCLUSION The CET + FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC. It facilitates the suppression of STMs, ameliorates the serum inflammatory microenvironment, and enhances QOL, without increased adverse drug effects.

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High Expression of Interleukin-2 Receptor Subunit Gamma Reveals Poor Prognosis in Human Gastric Cancer

Cited by 4 publications

References 24 publications

Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

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