&lt;p&gt;Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers&lt;/p&gt;

Liu, Fangteng; Wu, Hengyu

doi:10.2147/jir.s277353

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…The correlation module of TIMER (https://cistrome.shi nyapps.io/timer/) 19 was used for the correlation analysis between JAK expression and immune cell markers together with the Spearman's rho value and estimated statistical significance. The related gene markers of multiple immune cells were obtained from the related references [38][39][40] and the CellMarker database (http://biocc. hrbmu.edu.cn/CellMarker/).…”

Section: Correlation Analysis Between Jak Expression and Immune Cell mentioning

confidence: 99%

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer

Liu¹,

Wu²

2021

JIR

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Background: Janus kinases (JAKs) are a family of non-receptor tyrosine kinases involved in multiple malignancies. However, clinical values of JAKs as prognostic markers and potential mechanism as molecular targets in breast invasive carcinoma (BC) are not completely clarified. Methodology: TIMER, UALCAN and GEPIA were used to assess the expression and methylation levels of JAKs in BC. Kaplan-Meier Plotter, bc-GenExMiner, SurvExpress, TRGAted, MethSurv, and SurvivalMeth were used to assess the multilevel prognostic significance of JAKs in breast cancer patients. And cBioPortal, TIMER, STRING, GeneMANIA, NetworkAnalysis, LinkedOmics, DAVID 6.8, and Metascape were applied for multilayer networks and functional enrichment analyses. Correlations between immune cell infiltrates/their gene markers and JAKs were evaluated by TIMER. Results: We first explored the expression and methylation level of JAKs in breast cancer and found significantly reduced JAK1 and JAK2 expression at mRNA and protein levels, significantly higher JAK3 protein expression, and significantly increased TYK2 expression at mRNA level but decreased at protein level. In addition, hypermethylation of JAK3 and TYK2 and hypomethylation of JAK1 were found in tumor samples. In terms of prognostic values of JAKs in BC patients, low transcriptional levels of JAK1, JAK2, JAK3, and TYK2 indicated worse OS/DMFS/PPS/RFS/DFS, inferior DFS, worse RFS, and shorter OS/DMFS/ RFS, respectively. The mRNA signature analysis showed that high-risk group had unfavorable OS/RFS/MFS. Low JAK2 protein level indicated unfavorable DSS/PFS in BC patients. Five CpGs of JAK1, four CpGs of JAK2, 20 CpGs of JAK3, and 13 CpGs of TYK2 were significantly associated with prognosis in BC patients. The DNA methylation signature analysis also suggested worse prognosis in the high-risk group. For potential biological roles of JAKs, interaction analyses, functional enrichment analyses for biological process, cellular component, molecular function, and KEGG pathway analyses of JAKs and their neighbor genes in BC were conducted. Kinase targets, gene-miRNA interactions, and transcription factor-gene interactions of JAKs were also identified. Furthermore, JAKs were found to be significantly related to immune infiltrates as well as the expression levels of multiple immune markers in BC. Conclusion: JAKs showed multilevel prognostic value and important biological roles in BC. They might serve as promising prognostic markers and possible targets in breast cancer.

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Section: Correlation Analysis Between Jak Expression and Immune Cell mentioning

confidence: 99%

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer

Liu¹,

Wu²

2021

JIR

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“…Expression of GKN can be used as a good prognostic marker and therapeutic target for lung and stomach cancer, and the OS rate of patients with low GKN2 mRNA expression is poor [34,35]. The ectopic expression of GKN1 can inactivate the NF-κB signaling pathway and activate lκB to increase GKN2 expression by time-dependent means [36].…”

Section: Discussionmentioning

confidence: 99%

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients

Zou,

Xu,

et al. 2024

Int. J. Med. Sci.

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Background:The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results:In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

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“…Moreover, overexpressed MAT2A elevated the expression of RIP1 by increasing the H3K4 methylation at its promoter regions to induce the polarisation of M2 TAMs 47 . Several studies have demonstrated that the high expression of TUBA1A, ELK3, GKN2, COL1A2, RAI14, KIF23, GHRL, KCND2, SERPINE1, COL5A2, ALDOC and SLC38A2 and low expression of CD155 and AKR1B10 in GC indicate higher M2 TAM infiltration in the TME using data from public databases 93–107 . Furthermore, TAMs elevated the expression of PI3K‐γ by increasing the uptake of extracellular lipids, thereby inducing M2 phenotype polarisation 44 .…”

Section: The Role and Mechanism Of Tams In Gcmentioning

confidence: 99%

“… 47 Several studies have demonstrated that the high expression of TUBA1A, ELK3, GKN2, COL1A2, RAI14, KIF23, GHRL, KCND2, SERPINE1, COL5A2, ALDOC and SLC38A2 and low expression of CD155 and AKR1B10 in GC indicate higher M2 TAM infiltration in the TME using data from public databases. 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 Furthermore, TAMs elevated the expression of PI3K‐γ by increasing the uptake of extracellular lipids, thereby inducing M2 phenotype polarisation. 44 GC cells are characterised by enhanced glycolysis, producing large amounts of lactic acid that can induce the polarisation of M2 TAMs by activating the monocarboxylate channel transporter‐hypoxia inducible factor 1 subunit alpha (MCT–HIF1α) axis in macrophages.…”

Section: The Role and Mechanism Of Tams In Gcmentioning

confidence: 99%

Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

Li,

Sun,

Zeng

et al. 2023

Clinical & Translational Med

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BackgroundGastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence and development of GC is a complex process involving genetic changes in tumour cells and the influence of the surrounding tumour microenvironment (TME). Accumulative evidence shows that tumour‐associated macrophages (TAMs) play a vital role in GC, acting as plentiful and active infiltrating inflammatory cells in the TME.Main bodyIn this review, the different functions and mechanisms of TAMs in GC progression, including the conversion of phenotypic subtypes; promotion of tumour proliferation, invasion and migration; induction of chemoresistance; promotion of angiogenesis; modulation of immunosuppression; reprogramming of metabolism; and interaction with the microbial community are summarised. Although the role of TAMs in GC remains controversial in clinical settings, clarifying their significance in the treatment selection and prognostic prediction of GC could support optimising TAM‐centred clinicaltherapy.ConclusionIn summary, we reviewed the the phenotypic polarisation, function and molecular mechanism of TAMs and their potential applications in the treatment selection and prognostic prediction of GC.

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<p>Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers</p>

Cited by 7 publications

References 41 publications

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients

Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

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