IDO promotes the proliferation and invasion of prostate cancer cells through KYNU

Zhou, Huijie; Wang, Wei; Liu, Mingsheng; Xie, Pingbo; Deng, Tibin; Peng, Jiaxi; Xu, Chen-Xiang

doi:10.1007/s13258-022-01316-y

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…KYNU encodes kynureninase, an enzyme that catalyzes the cleavage of L-kynurenine, which has been found to block cytokine-mediated up-regulation of the expression and function of NKp46 and NKG2D, thereby inducing NK cell-mediated killing 50 . In addition, high expression levels of KYNU were previously shown to be related to poor disease-free survival in cancer patients 51 . It has been reported that the depletion of KYNU could inhibit the growth of cancer cells via the PI3K/AKT signaling pathway 52 .…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Sun,

Kong,

et al. 2024

Sci Rep

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Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Sun,

Kong,

et al. 2024

Sci Rep

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“…MSI2 has the potential to be a novel therapeutic target for cancers [39] and can promote cancer progression and drug resistance via multiple signaling pathways [40][41][42][43][44]. High expression levels of KYNU were previously shown to be related to poor disease-free survival in cancer patients [45]. It has been reported that the depletion of KYNU could inhibit the growth of cancer cells via the PI3K/AKT signaling pathway [46].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Sun,

Kong,

et al. 2024

Preprint

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Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1187 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8 + T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

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“…In squamous carcinoma, KYNU overexpression promotes cancer cell proliferation and invasion through the PI3K/ AKT pathway [10]. Zhou et al confirmed through in vitro experiments that silencing KYNU significantly inhibited the tumor-promoting effects of indoleamine-2,3-dioxygenase on prostate cancer cells [11]. However, there are few reports on whether KYNU is a prognostic biomarker of GC.…”

Section: Introductionmentioning

confidence: 99%

KYNU as a Biomarker of Tumor-Associated Macrophages and Correlates with Immunosuppressive Microenvironment and Poor Prognosis in Gastric Cancer

Shen,

Chen,

Yang

et al. 2023

International Journal of Genomics

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Background. Kynureninase (KYNU) is a potential prognostic marker for various tumor types. However, no reports on the biological effects and prognostic value of KYNU in gastric cancer (GC) exist. Methods. GC-associated single-cell RNA sequencing and bulk RNA sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of KYNU between GC and normal gastric tissues was first analyzed based on the bulk-seq data, followed by an exploration of the relationship between KYNU and various clinicopathological features. The Kaplan–Meier survival and Cox regression analyses were performed to determine the prognostic value of KYNU. The relationship between KYNU expression and immune cell infiltration and immune checkpoints was also explored. The biological function of KYNU was further examined at the single-cell level, and in vitro experiments were performed to examine the effect of KYNU on GC cell proliferation and invasion. Results. KYNU expression was significantly elevated in GC samples. Clinical features and survival analysis indicated that high KYNU expression was associated with poor clinical phenotypes and prognosis, whereas Cox analysis showed that KYNU was an independent risk factor for patients with GC. Notably, high expression of KYNU induced a poor immune microenvironment and contributed to the upregulation of immune checkpoints. KYNU-overexpressing macrophages drove GC progression through unique ligand-receptor pairs and transcription factors and were associated with adverse clinical phenotypes in GC. KYNU was overexpressed in GC cells in vitro, and KYNU knockout significantly inhibited GC cell proliferation and invasion. Conclusion. High KYNU expression promotes an adverse immune microenvironment and low survival rates in GC. KYNU and KYNU-related macrophages may serve as novel molecular targets in the treatment of GC.

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IDO promotes the proliferation and invasion of prostate cancer cells through KYNU

Cited by 3 publications

References 27 publications

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

KYNU as a Biomarker of Tumor-Associated Macrophages and Correlates with Immunosuppressive Microenvironment and Poor Prognosis in Gastric Cancer

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