Decreased Expression of Selenoproteins as a Poor Prognosticator of Gastric Cancer in Humans

Lan, Xiuwen; Xing, Jun; Gao, Hongyu; Li, Sen; Quan, Lina; Jiang, Yang; Ding, Shaohua; Xue, Yingwei

doi:10.1007/s12011-016-0908-8

Cited by 29 publications

(20 citation statements)

References 26 publications

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“…High levels of GPX3 expression associated with poor survival in stomach adenocarcinoma may act through PI3K/AKT activation. Recently, it was shown that SELENOM and SELENOW were significantly decreased in gastric cancer in Harbin, China ( 59 ). Downregulation of SELENBP1 and associated poor survival were also observed in stomach adenocarcinoma in Wuhan, China ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Potential relationship between the selenoproteome and cancer

2020

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The role of the selenoproteome, which is the collection of all proteins containing selenium in an organism, in cancer development, growth and progression requires further investigation, due to the importance of selenium in both cancer and immune system function. Data about the selenoproteome, including its differential expression, single nucleotide variations, copy number variations, methylation, pathways and overall survival (OS) in five leading types of cancer are available from the GSCALite website. Subsequent to the analysis of these datasets, it was revealed that there was increased expression of GPX3 in stomach adenocarcinoma and lung squamous cell carcinoma, SELENOV in oesophageal carcinoma, GPX8 and GPX4 in colon adenocarcinoma, TXNRD1 and SEPHS1 in hepatocellular carcinoma and GPX8 in lung adenocarcinoma were associated with poor survival. Decreased gene expression of SELENOP was indicated in liver hepatocellular carcinoma and GPX3, and SELENOW, SELENOK, SELENBP1 and SECISBP2 in lung adenocarcinoma were associated with a poor prognosis. OS data suggested that hypermethylation of GPX4 in colon adenocarcinoma, GPX8 in lung squamous cell carcinoma, GPX1 in stomach adenocarcinoma and GPX3 in lung adenocarcinoma was associated with low survival, as is hypomethylation of GPX5 in lung adenocarcinoma. The selenoproteome is heterogeneous, especially in its effect on the OS of patients with cancer. The present study demonstrated that the roles of GPX4 in colon adenocarcinoma, SCLY and SELENOV in oesophageal carcinoma, SEPHS1 in liver hepatocellular carcinoma, SELENOK in lung cancer, as well as SELENOM and SELENOW in stomach adenocarcinoma requires further research. The present study may lead to the identification of novel biomarkers or potential therapeutic targets for use in the treatment of cancers, such as colon adenocarcinoma, oesophageal carcinoma, liver hepatocellular carcinoma, lung cancer and stomach adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Potential relationship between the selenoproteome and cancer

2020

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“…Almost all normal mammalian cells show GPX4 activity, particularly abundant in testis, adipose tissue and retina [30,31]. However, GPX4 is hardly detectable in lymphocytes by immunohistochemistry [32] and has decreased expression at the mRNA level [21], though its enzymatic activity is detected to some extent [33].…”

Section: Discussionmentioning

confidence: 99%

“…Although there are few reports of GPX4 in tumor tissue, GPX4 was found to be increased in colon carcinomas [15] and in hepatocellular carcinomas [16], and decreased GPX4 level has been reported in pancreatic cancer [17], breast cancer cells [18], clear cell renal cell carcinomas [19], and gastric cancer [21]. A variant of the gene encoding GPX4 has been reported to influence prostate cancer risk [20].…”

Section: Discussionmentioning

confidence: 99%

“…The GPX family member GPX4, also known as phospholipid-hydroperoxide glutathione peroxidase, is considered one of the most important antioxidant enzymes in mammals [12][13][14]. Recently, there have been reports suggesting that overexpression or depletion of GPX4 is responsible for tumorigenesis and tumor progression [15][16][17][18][19][20][21]. However, the frequency of GPX4 expression in malignant lymphoma including DLBCL, its histological relevance, and its relevance prognosis are not currently known.…”

Section: Introductionmentioning

confidence: 99%

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Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma

Kinowaki

Kurata

Ishibashi

et al. 2018

Laboratory Investigation

113

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Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

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“…Gene symbols Membrane ACKR1, ADGRB3, CHRNA3 [23], CYP1B1 [24], FLNC [25], PLIN4, PLN, RNF150, SELP [26], TACR2…”

Section: Categoriesmentioning

confidence: 99%

Exploring TCGA database for identification of potential prognostic genes in stomach adenocarcinoma

Zhou

Huang

et al. 2020

Cancer Cell Int

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Background: Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer in the world and ranks third among cancer-related deaths worldwide. The tumour microenvironment (TME) plays an important role in tumorigenesis, development, and metastasis. Hence, we calculated the immune and stromal scores to find the potential prognosisrelated genes in STAD using bioinformatics analysis. Methods: The ESTIMATE algorithm was used to calculate the immune/stromal scores of the STAD samples. Functional enrichment analysis, protein-protein interaction (PPI) network analysis, and overall survival analysis were then performed on differential genes. And we validated these genes using data from the Gene Expression Omnibus database. Finally, we used the Human Protein Atlas (HPA) databases to verify these genes at the protein levels by IHC. Results: Data analysis revealed correlation between stromal/immune scores and the TNM staging system. The top 10 core genes extracted from the PPI network, and primarily involved in immune responses, extracellular matrix, and cell adhesion. There are 31 genes have been validated with poor prognosis and 16 genes were upregulated in tumour tissues compared with normal tissues at the protein level. Conclusions: In summary, we identified genes associated with the tumour microenvironment with prognostic implications in STAD, which may become potential therapeutic markers leading to better clinical outcomes.

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Decreased Expression of Selenoproteins as a Poor Prognosticator of Gastric Cancer in Humans

Cited by 29 publications

References 26 publications

Potential relationship between the selenoproteome and cancer

Potential relationship between the selenoproteome and cancer

Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma

Exploring TCGA database for identification of potential prognostic genes in stomach adenocarcinoma

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