Association between GPX3 promoter methylation and malignant tumors: A meta-analysis

Zhou, Cong; Hu, Haochang; Zheng, Zhangqian; Chen, Chujia; Li, Yin; Li, Bin; Duan, Shiwei

doi:10.1016/j.prp.2019.152443

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…5-year OS was about 50% in the high-risk group and 75% in the low-risk group, which was consistent with previous reports (Dueland et al 2018). High-risk genes in the model, including GPX3, AKR1C4, SPHK1and ADCY5, have been reported to promote hypermethylation, rare mutations, cancer progression, poor prognosis, and the developmental process of malignant cells in CRC patient samples or cell lines (Gylfe et al 2013;Kawamori et al 2009;Liang et al 2013;Pan et al 2019;Zhou et al 2019).…”

Section: Discussionsupporting

confidence: 91%

Peer Review #3 of "Prognostic implications of metabolism-associated gene signatures in colorectal cancer (v0.2)"

2020

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Colorectal cancer (CRC) is one of the most common and deadly malignancies. Novel biomarkers for the diagnosis and prognosis of this disease must be identified. Besides, metabolism plays an essential role in the occurrence and development of CRC. This article aims to identify some critical prognosis-related metabolic genes (PRMGs) and construct a prognosis model of CRC patients for clinical use. We obtained the expression profiles of CRC from The Cancer Genome Atlas database (TCGA), then identified differentially expressed PRMGs by R and Perl software. Hub genes were filtered out by univariate Cox analysis and least absolute shrinkage and selection operator Cox analysis. We used functional enrichment analysis methods, such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, to identify involved signaling pathways of PRMGs. The nomogram predicted overall survival (OS) Calibration traces were used to evaluate the consistency between the actual and the predicted survival rate. Finally, a prognostic model was constructed based on six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK1, and ADCY5), and the risk score was an independent prognostic prognosticator. Genetic expression and risk score were significantly correlated with clinicopathologic characteristics of CRC. A nomogram based on the clinicopathological feature of CRC and risk score accurately predicted the OS of individual CRC cancer patients. We also validated the results in the independent colorectal cancer cohorts GSE39582 and GSE87211. Our study demonstrates that the risk score is an independent prognostic biomarker and is closely correlated with the malignant clinicopathological characteristics of CRC patients. We also determined some metabolic genes associated with the survival and clinical stage of CRC as potential biomarkers for CRC diagnosis and treatment.

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Section: Discussionsupporting

confidence: 91%

Peer Review #3 of "Prognostic implications of metabolism-associated gene signatures in colorectal cancer (v0.2)"

2020

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“…5-year OS was about 50% in the high-risk group and 75% in the low-risk group, which was consistent with previous reports ( Dueland et al, 2018 ). High-risk genes in the model, including GPX3, AKR1C4, SPHK1and ADCY5, have been reported to promote hypermethylation, rare mutations, cancer progression, poor prognosis, and the developmental process of malignant cells in CRC patient samples or cell lines ( Gylfe et al, 2013 ; Kawamori et al, 2009 ; Liang et al, 2013 ; Pan et al, 2019 ; Zhou et al, 2019 ). SPHK1 promotes the phosphorylation and activation of p65, thus promoting the occurrence of CRC ( Shen et al, 2019b ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of metabolism-associated gene signatures in colorectal cancer

Miao

Wang

et al. 2020

PeerJ

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Colorectal cancer (CRC) is one of the most common and deadly malignancies. Novel biomarkers for the diagnosis and prognosis of this disease must be identified. Besides, metabolism plays an essential role in the occurrence and development of CRC. This article aims to identify some critical prognosis-related metabolic genes (PRMGs) and construct a prognosis model of CRC patients for clinical use. We obtained the expression profiles of CRC from The Cancer Genome Atlas database (TCGA), then identified differentially expressed PRMGs by R and Perl software. Hub genes were filtered out by univariate Cox analysis and least absolute shrinkage and selection operator Cox analysis. We used functional enrichment analysis methods, such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, to identify involved signaling pathways of PRMGs. The nomogram predicted overall survival (OS). Calibration traces were used to evaluate the consistency between the actual and the predicted survival rate. Finally, a prognostic model was constructed based on six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK1, and ADCY5), and the risk score was an independent prognostic prognosticator. Genetic expression and risk score were significantly correlated with clinicopathologic characteristics of CRC. A nomogram based on the clinicopathological feature of CRC and risk score accurately predicted the OS of individual CRC cancer patients. We also validated the results in the independent colorectal cancer cohorts GSE39582 and GSE87211. Our study demonstrates that the risk score is an independent prognostic biomarker and is closely correlated with the malignant clinicopathological characteristics of CRC patients. We also determined some metabolic genes associated with the survival and clinical stage of CRC as potential biomarkers for CRC diagnosis and treatment.

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“…Proteomics analysis on the cerebrospinal fluids of the extranodal NK-/T-cell lymphomas patients has identified GPX3 as a predictor of metastatic disease [ 46 ]. Hypermethylation of GPX3 has also been reported as a cancer risk factor [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Increased glutathione utilization augments tumor cell proliferation in Waldenstrom Macroglobulinemia

Jalali

Shi

Buko³

et al. 2020

Redox Biology

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Metabolic reprogramming is a hallmark of cancer cells. In Waldenstrom Macroglobulinemia (WM), the infiltration of IgM-secreting lymphoplamacytic cells into the bone marrow (BM) could shift the homeostasis of proteins and metabolites towards a permissive niche for tumor growth. Here, we investigated whether alerted metabolic pathways contribute to the pathobiology of WM and whether the cytokine composition of the BM promotes such changes. Metabolomics analysis on WM patients and normal donors’ serum samples revealed a total of 75 metabolites that were significantly altered between two groups. While these metabolites belonged to amino acids, glucose, glutathione and lipid metabolism pathways, the highest number of the differentially expressed metabolites belonged to glutathione metabolism. Proteomics analysis and immunohistochemical staining both confirmed the increased protein levels mediating glutathione metabolism, including GCLC, MT1X, QPCT and GPX3. Moreover, treatment with IL-6 and IL-21, cytokines that induce WM cell proliferation and IgM secretion, increased gene expression of the amino acid transporters mediating glutathione metabolism, including ASCT2, SLC7A11 and 4F2HC, indicating that cytokines in the WM BM could modulate glutathione metabolism. Glutathione synthesis inhibition using Buthionine sulphoximine (BSO) significantly reduced WM cells proliferation in vitro , accompanied with decreased NFκB-p65 and MAPK-p38 phosphorylation. Moreover, BSO treatment significantly reduced the tumor growth rate in a WM xenograft model, further highlighting the role of glutathione metabolism in promoting tumor growth and proliferation. In summary, our data highlight a central role for glutathione metabolism in WM pathobiology and indicate that intervening with the metabolic processes could be a potential therapy for WM patients.

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Association between GPX3 promoter methylation and malignant tumors: A meta-analysis

Cited by 13 publications

References 31 publications

Peer Review #3 of "Prognostic implications of metabolism-associated gene signatures in colorectal cancer (v0.2)"

Peer Review #3 of "Prognostic implications of metabolism-associated gene signatures in colorectal cancer (v0.2)"

Prognostic implications of metabolism-associated gene signatures in colorectal cancer

Increased glutathione utilization augments tumor cell proliferation in Waldenstrom Macroglobulinemia

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