Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration and invasion of human hepatocellular carcinoma

Jin, Haojie; Zhang, Yurong; You, Hyun Ju; Tao, Xuemei; Wang, Cun; Jin, Guang‐Zhi; Wang, Ning; Ruan, Haoyu; Gu, Danan; Huo, Xisong; Wang, Cong; Qin, Wenxin

doi:10.1038/srep10466

Cited by 62 publications

(60 citation statements)

References 48 publications

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“…Also, KMO activity may be involved in tumor immune tolerance. Recent studies have shown that its overexpression is related to rapid cancer progression and a poor prognosis (49,180). Similar to inflammatory-induced IDO1 expression, KMO expression is induced by inflammatory stimuli (181,182).…”

Section: Indoleamine 23-dioxygenase 2 Tryptophan 23-dioxygenase Amentioning

confidence: 97%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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Section: Indoleamine 23-dioxygenase 2 Tryptophan 23-dioxygenase Amentioning

confidence: 97%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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“…MZ‐1, a neutralizing monoclonal antibody to POSTN, showed significant growth inhibition both in vivo and in vitro, thereby providing an alternative approach in clinical management of CE patients. KMO is a pivotal enzyme in the kynurenine‐mediated tryptophan degradation pathway; it positively regulates proliferation, migration, and invasion of tumor cells, and may serve as a novel prognostic marker in various cancers . Recently, investigators revealed the crystal structure of Saccharomyces cerevisiae KMO, in the free form and in complex with the tight‐binding inhibitor UPF 648, which will promote the search for new KMO inhibitors in targeted therapies against neurodegenerative diseases and tumor.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas

Liu

Sun

et al. 2018

Cancer Medicine

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The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1‐weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis (GSEA), significant analysis of microarray, generalized linear models, and Least absolute shrinkage and selection operator algorithm were used to explore radiogenomic and prognostic signatures of AG patients. GSEA indicated that angiogenesis and epithelial‐mesenchymal transition were significantly associated with post‐CE. Genes driving immune system response, cell proliferation, and focal adhesions were also significantly enriched. Gene ontology of 237 differential genes indicated consistent results. A 48‐gene signature for CE was identified in TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore, seven genes derived from the CE‐specific signature could stratify AG patients into two subgroups based on overall survival time according to corresponding risk score. Comprehensive analysis of post‐CE and genomic characteristics leads to a better understanding of radiology‐pathology correlations. Our gene signature helps interpret the occurrence of radiological traits and predict clinical outcomes. Additionally, we found nine prognostic quantitative radiomic features of CE and investigated the underlying biological processes of them.

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“…Jin et al () detected the expression of KMO in HCC by immunohistochemistry. In vitro studies showed that KMO can absolutely regulate the proliferation, migration, and invasion of HCC cells.…”

Section: The Mechanism Of Kmo In Different Diseasesmentioning

confidence: 99%

“…However, human pancreatitis is highly heterogeneous, so further studies are necessary to demonstrate whether KMO inhibitors are suitable for all pancreatitis (Ray, 2016). Jin et al (2015) detected the expression of KMO in HCC by immunohistochemistry. In vitro studies showed that KMO can absolutely regulate the proliferation, migration, and invasion of HCC cells.…”

Section: Non-neurological Diseasementioning

confidence: 99%

Kynurenine‐3‐monooxygenase: A new direction for the treatment in different diseases

Lü

Shao

2020

Food Science & Nutrition

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Kynurenine‐3‐monooxygenase (KMO) is an enzyme that relies on nicotinamide adenine dinucleotide phosphate (NADP), a key site in the kynurenine pathway (KP), which has great effects on neurological diseases, cancer, and peripheral inflammation. This review mainly pay attention to the research of KMO mechanism for the treatment of different diseases, and hopes to provide assistance for clinical and drug use. KMO controlling the chief division of the KP, which directly controls downstream product quinolinic acid (QUIN) and indirectly controls kynurenic acid (KYNA), plays an important role in many diseases, especially neurological diseases.

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Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration and invasion of human hepatocellular carcinoma

Cited by 62 publications

References 48 publications

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas

Kynurenine‐3‐monooxygenase: A new direction for the treatment in different diseases

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