The Multi-Omic Prognostic Model of Oxidative Stress-Related Genes in Acute Myeloid Leukemia

Dong, Chao; Zhang, Naijin; Zhang, Lijun

doi:10.3389/fgene.2021.722064

Cited by 11 publications

(4 citation statements)

References 55 publications

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“…Oxidative stress-related signatures have been established in acute myeloid leukemia ( Dong et al, 2021 ), melanoma ( Yang et al, 2021 ), clear-cell renal cell carcinoma ( Wu Y. et al, 2021a ), gastric cancer ( Wu Z. et al, 2021b ), head and neck squamous cell carcinoma ( Wang and Zhou, 2021 ), glioma ( Lu et al, 2021 ), and bladder cancer ( Zhang et al, 2022 ). Alterations in redox status accompanied by increased production of ROS have been implicated in CRC ( Lee et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer

Cao

Chen²,

Gu³

et al. 2023

Front. Pharmacol.

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Objective: Accumulated evidence highlights the biological significance of oxidative stress in tumorigenicity and progression of colorectal cancer (CRC). Our study aimed to establish a reliable oxidative stress-related signature to predict patients’ clinical outcomes and therapeutic responses.Methods: Transcriptome profiles and clinical features of CRC patients were retrospectively analyzed from public datasets. LASSO analysis was used to construct an oxidative stress-related signature to predict overall survival, disease-free survival, disease-specific survival, and progression-free survival. Additionally, antitumor immunity, drug sensitivity, signaling pathways, and molecular subtypes were analyzed between different risk subsets through TIP, CIBERSORT, oncoPredict, etc. approaches. The genes in the signature were experimentally verified in the human colorectal mucosal cell line (FHC) along with CRC cell lines (SW-480 and HCT-116) through RT-qPCR or Western blot.Results: An oxidative stress-related signature was established, composed of ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CDKN2A, CRYAB, NGFR, and UCN. The signature displayed an excellent capacity for survival prediction and was linked to worse clinicopathological features. Moreover, the signature correlated with antitumor immunity, drug sensitivity, and CRC-related pathways. Among molecular subtypes, the CSC subtype had the highest risk score. Experiments demonstrated that CDKN2A and UCN were up-regulated and ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CRYAB, and NGFR were down-regulated in CRC than normal cells. In H2O2-induced CRC cells, their expression was notably altered.Conclusion: Altogether, our findings constructed an oxidative stress-related signature that can predict survival outcomes and therapeutic response in CRC patients, thus potentially assisting prognosis prediction and adjuvant therapy decisions.

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Section: Discussionmentioning

confidence: 99%

Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer

Cao

Chen²,

Gu³

et al. 2023

Front. Pharmacol.

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“…GSEA ( https://www.gsea-msigdb.org/gsea/login.jsp ) was performed using the “kegg.v7.4.symbols.gmt” gene set to identify significantly enriched pathways between the low- and high-risk groups. Pathways with P < 0.05 and FDR < 0.25 were regarded as significantly enriched pathways [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer

Chen

Wei

2023

BMC Bioinformatics

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Background Colorectal cancer (CRC) is one of the most common cancers in the world. Oxidative stress reactions have been reportedly associated with oncogenesis and tumor progression. By analyzing mRNA expression data and clinical information from The Cancer Genome Atlas (TCGA), we aimed to construct an oxidative stress-related long noncoding RNA (lncRNA) risk model and identify oxidative stress-related biomarkers to improve the prognosis and treatment of CRC. Results Differentially expressed oxidative stress-related genes (DEOSGs) and oxidative stress-related lncRNAs were identified by using bioinformatics tools. An oxidative stress-related lncRNA risk model was constructed based on 9 lncRNAs (AC034213.1, AC008124.1, LINC01836, USP30-AS1, AP003555.1, AC083906.3, AC008494.3, AC009549.1, and AP006621.3) by least absolute shrinkage and selection operator (LASSO) analysis. The patients were then divided into high- and low-risk groups based on the median risk score. The high-risk group had a significantly worse overall survival (OS) (p < 0.001). Receiver operating characteristic (ROC) and calibration curves displayed the favorable predictive performance of the risk model. The nomogram successfully quantified the contribution of each metric to survival, and the concordance index and calibration plots demonstrated its excellent predictive capacity. Notably, different risk subgroups showed significant differences in terms of their metabolic activity, mutation landscape, immune microenvironment and drug sensitivity. Specifically, differences in the immune microenvironment implied that CRC patients in certain subgroups might be more responsive to immune checkpoint inhibitors. Conclusions Oxidative stress-related lncRNAs can predict the prognosis of CRC patients, which provides new insight for future immunotherapies based on potential oxidative stress targets.

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“…In turn, NADP + which is generated both by NADPH oxidases and by the leukemia cells' antioxidant systems is essential for the activity of ALDH enzymes. Specific patterns of dysregulation of oxidant stress and inflammatorymetabolic regulatory networks are associated with worse clinical outcomes in AML; this is also evident by the fact that levels of advanced oxidation protein products, malondialdehyde, and 8-hydroxydeoxyguanosine are also significantly higher in relapsed AML patients [107][108][109].…”

Section: Aml Poor Prognosis and Coordination Of Cellular Turnover And...mentioning

confidence: 99%

The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia

Dancik

Varisli

Vlahopoulos

2023

IJMS

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The protein family of aldehyde dehydrogenases (ALDH) encompasses nineteen members. The ALDH1 subfamily consists of enzymes with similar activity, having the capacity to neutralize lipid peroxidation products and to generate retinoic acid; however, only ALDH1A1 emerges as a significant risk factor in acute myeloid leukemia. Not only is the gene ALDH1A1 on average significantly overexpressed in the poor prognosis group at the RNA level, but its protein product, ALDH1A1 protects acute myeloid leukemia cells from lipid peroxidation byproducts. This capacity to protect cells can be ascribed to the stability of the enzyme under conditions of oxidant stress. The capacity to protect cells is evident both in vitro, as well as in mouse xenografts of those cells, shielding cells effectively from a number of potent antineoplastic agents. However, the role of ALDH1A1 in acute myeloid leukemia has been unclear in the past due to evidence that normal cells often have higher aldehyde dehydrogenase activity than leukemic cells. This being true, ALDH1A1 RNA expression is significantly associated with poor prognosis. It is hence imperative that ALDH1A1 is methodically targeted, particularly for the acute myeloid leukemia patients of the poor prognosis risk group that overexpress ALDH1A1 RNA.

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The Multi-Omic Prognostic Model of Oxidative Stress-Related Genes in Acute Myeloid Leukemia

Cited by 11 publications

References 55 publications

Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer

Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer

The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia

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