Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients

Liu, Yanchen; Li, Mengyun; Shi, Danping; Zhu, Yushan

doi:10.1007/s10792-019-01129-1

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…CHAC1 is a new pro-apoptotic member of the unfolded protein response pathway and is intimately related to failed chemotherapy ( Shuda et al, 2003 ; Scriven et al, 2009 ; Goebel et al, 2012 ). Previously, only Yanchen Liu indicated that the mRNA expression of CHAC1 was associated with poor OS and high risk of metastasis in a limited number of samples from 34 patients ( Liu et al, 2019 ). In the present study, we re-validated the conclusion above in four datasets and further discovered a relationship between CHAC1 and the immune signature of UVM, illustrating the innate mechanisms by which CHAC1 exerts a harmful influence on clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma

Jin

Wang

et al. 2021

Front. Cell Dev. Biol.

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Uveal melanoma (UVM) is an intraocular malignancy in adults in which approximately 50% of patients develop metastatic disease and have a poor prognosis. The need for immunotherapies has rapidly emerged, and recent research has yielded impressive results. Emerging evidence has implicated ferroptosis as a novel type of cell death that may mediate tumor-infiltrating immune cells to influence anticancer immunity. In this study, we first selected 11 ferroptosis regulators in UVM samples from the training set (TCGA and GSE84976 databases) by Cox analysis. We then divided these molecules into modules A and B based on the STRING database and used consensus clustering analysis to classify genes in both modules. According to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the results revealed that the clusters in module A were remarkably related to immune-related pathways. Next, we applied the ESTIMATE and CIBERSORT algorithms and found that these ferroptosis-related patterns may affect a proportion of TME infiltrating cells, thereby mediating the tumor immune environment. Additionally, to further develop the prognostic signatures based on the immune landscape, we established a six-gene-regulator prognostic model in the training set and successfully verified it in the validation set (GSE44295 and GSE27831). Subsequently, we identified the key molecules, including ABCC1, CHAC1, and GSS, which were associated with poor overall survival, progression-free survival, disease-specific survival, and progression-free interval. We constructed a competing endogenous RNA network to further elucidate the mechanisms, which consisted of 29 lncRNAs, 12 miRNAs, and 25 ferroptosis-related mRNAs. Our findings indicate that the ferroptosis-related genes may be suitable potential biomarkers to provide novel insights into UVM prognosis and decipher the underlying mechanisms in tumor microenvironment characterization.

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Section: Discussionmentioning

confidence: 99%

Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma

Jin

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…CHAC1 was a novel proapoptotic member of ER stressrelated genes and possessed γ-glutamyl cyclotransferase activity, thus regulating the degradation of GSH (Cui et al, 2021). Previous research studies suggested that CHAC1 was correlated with a high risk of metastasis and poor prognosis and exerted a harmful influence on clinical outcomes in uveal melanoma (Liu et al, 2019). As reported, tumors should adapt to the ER stress mechanisms which contained the unfolded protein response (UPR) and the ER-associated degradation (ERAD) to keep protein homeostasis if they were to survive and grow.…”

Section: Discussionmentioning

confidence: 99%

Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma

Shen

Cao

Zhou

et al. 2022

Front. Mol. Biosci.

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Background: Kidney renal clear cell carcinoma (KIRC) is one of the most lethal malignant tumors with a propensity for poor prognosis and difficult treatment. Endoplasmic reticulum (ER) stress served as a pivotal role in the progression of the tumor. However, the implications of ER stress on the clinical outcome and immune features of KIRC patients still need elucidation.Methods: We identified differentially expressed ER stress-related genes between KIRC specimens and normal specimens with TCGA dataset. Then, we explored the biological function and genetic mutation of ER stress-related differentially expressed genes (DEGs) by multiple bioinformatics analysis. Subsequently, LASSO analysis and univariate Cox regression analysis were applied to construct a novel prognostic model based on ER stress-related DEGs. Next, we confirmed the predictive performance of this model with the GEO dataset and explored the potential biological functions by functional enrichment analysis. Finally, KIRC patients stratified by the prognostic model were assessed for tumor microenvironment (TME), immune infiltration, and immune checkpoints through single-sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE analysis.Results: We constructed a novel prognostic model, including eight ER stress-related DEGs, which could stratify two risk groups in KIRC. The prognostic model and a model-based nomogram could accurately predict the prognosis of KIRC patients. Functional enrichment analysis indicated several biological functions related to the progression of KIRC. The high-risk group showed higher levels of tumor infiltration by immune cells and higher immune scores.Conclusion: In this study, we constructed a novel prognostic model based on eight ER stress-related genes for KIRC patients, which would help predict the prognosis of KIRC and provide a new orientation to further research studies on personalized immunotherapy in KIRC.

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“…Similarly, ATF6a can phosphorylate and activate AKT in intestinal epithelial cells [ 149 ]. ER stress also inactivates AKT to up-regulate CHOP expression and induce cell death [ 150 ]. Alkylphosphocholine erufosine, an AKT-mTOR inhibitor, induces ROS generation and ER stress in oral cancer cells [ 180 ].…”

Section: Akt Modulates Cell Functionsmentioning

confidence: 99%

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

et al. 2022

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Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.

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Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients

Cited by 20 publications

References 24 publications

Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma

Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma

Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

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