P2RY14 Is a Potential Biomarker of Tumor Microenvironment Immunomodulation and Favorable Prognosis in Patients With Head and Neck Cancer

Li, Qingxiang; Xu, Le; Li, Yuke; Yang, Rong; Qiao, Qiao; Wang, Yifei; Wang, Lin; Guo, Yuxing; Guo, Chuanbin

doi:10.3389/fgene.2021.670746

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…P2RY14 is a UDP-glucose P2Y purinergic receptor that plays a crucial role in signaling through G-protein-coupled receptors and peptide ligand-binding receptors ( 34 ). It is associated with various biological processes, including immune responses, tumorigenesis and cell senescence ( 35 , 36 ).…”

Section: Resultsmentioning

confidence: 99%

Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis

Zhou,

Wang,

et al. 2023

Oncol Lett

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The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis.

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Section: Resultsmentioning

confidence: 99%

Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis

Zhou,

Wang,

et al. 2023

Oncol Lett

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“…The results of the differential analysis showed that all 11 genes differed in tumor and normal tissues, and we finally selected P2RY14 for experimental study.P2RY14 is thought to be potentially associated with immune invasion in lung cancer and plays an important role in suppressing immune escape of tumor cells within the lung cancer microenvironment ( 41 ). In head and neck cancer, P2RY14 is also a potential biomarker for immune regulation of the tumor microenvironment and good prognosis ( 42 ). In addition, more meta-analyses have shown that potentially functional polymorphisms of IL12A and IL12B are thought to increase the risk of malignancies such as gastric, lung, and cervical cancers ( 43 – 45 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer

et al. 2023

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BackgroundOvarian cancer (OC) is one of the most common and most malignant gynecological malignancies in gynecology. On the other hand, dysregulation of copper metabolism (CM) is closely associated with tumourigenesis and progression. Here, we investigated the impact of genes associated with copper metabolism (CMRGs) on the prognosis of OC, discovered various CM clusters, and built a risk model to evaluate patient prognosis, immunological features, and therapy response.Methods15 CMRGs affecting the prognosis of OC patients were identified in The Cancer Genome Atlas (TCGA). Consensus Clustering was used to identify two CM clusters. lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters. The GSE63885 cohort was used as an external validation cohort. Expression of CM risk score-associated genes was verified by single-cell sequencing and quantitative real-time PCR (qRT-PCR). Nomograms were used to visually depict the clinical value of CMRGPS. Differences in clinical traits, immune cell infiltration, and tumor mutational load (TMB) between risk groups were also extensively examined. Tumour Immune Dysfunction and Rejection (TIDE) and Immune Phenotype Score (IPS) were used to validate whether CMRGPS could predict response to immunotherapy in OC patients.ResultsIn the TCGA and GSE63885 cohorts, we identified two CM clusters that differed significantly in terms of overall survival (OS) and tumor microenvironment. We then created a CMRGPS containing 11 genes to predict overall survival and confirmed its reliable predictive power for OC patients. The expression of CM risk score-related genes was validated by qRT-PCR. Patients with OC were divided into low-risk (LR) and high-risk (HR) groups based on the median CM risk score, with better survival in the LR group. The 5-year AUC value reached 0.74. Enrichment analysis showed that the LR group was associated with tumor immune-related pathways. The results of TIDE and IPS showed a better response to immunotherapy in the LR group.ConclusionOur study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of patients with OC, offering new insights into individualized treatment.

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“…Other genes related to immune functions were KLRD1, NOTCH3 and TCF7L1 (Supplementary Table 7). Furthermore, the following genes CAPG, DNTT, KCNIP3, and P2RY14 have also been reported in the literature to be related to immunity (30)(31)(32).…”

Section: Genes Differentially Expressed Between Groups Diverging In P...mentioning

confidence: 91%

Genetic architecture of innate and adaptive immune cells in pigs

Ballester

Jové-Juncà²,

Pascual³

et al. 2023

Front. Immunol.

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Pig industry is facing new challenges that make necessary to reorient breeding programs to produce more robust and resilient pig populations. The aim of the present work was to study the genetic determinism of lymphocyte subpopulations in the peripheral blood of pigs and identify genomic regions and biomarkers associated to them. For this purpose, we stained peripheral blood mononuclear cells to measure ten immune-cell-related traits including the relative abundance of different populations of lymphocytes, the proportions of CD4+ T cells and CD8+ T cells, and the ratio of CD4+/CD8+ T cells from 391 healthy Duroc piglets aged 8 weeks. Medium to high heritabilities were observed for the ten immune-cell-related traits and significant genetic correlations were obtained between the proportion of some lymphocytes populations. A genome-wide association study pointed out 32 SNPs located at four chromosomal regions on pig chromosomes SSC3, SSC5, SSC8, and SSCX as significantly associated to T-helper cells, memory T-helper cells and γδ T cells. Several genes previously identified in human association studies for the same or related traits were located in the associated regions, and were proposed as candidate genes to explain the variation of T cell populations such as CD4, CD8A, CD8B, KLRC2, RMND5A and VPS24. The transcriptome analysis of whole blood samples from animals with extreme proportions of γδ T, T-helper and memory T-helper cells identified differentially expressed genes (CAPG, TCF7L1, KLRD1 and CD4) located into the associated regions. In addition, differentially expressed genes specific of different T cells subpopulations were identified such as SOX13 and WC1 genes for γδ T cells. Our results enhance the knowledge about the genetic control of lymphocyte traits that could be considered to optimize the induction of immune responses to vaccines against pathogens. Furthermore, they open the possibility of applying effective selection programs for improving immunocompetence in pigs and support the use of the pig as a very reliable human biomedical model.

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P2RY14 Is a Potential Biomarker of Tumor Microenvironment Immunomodulation and Favorable Prognosis in Patients With Head and Neck Cancer

Cited by 9 publications

References 28 publications

Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis

Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis

Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer

Genetic architecture of innate and adaptive immune cells in pigs

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