Glutathione Peroxidase 8 as a Prognostic Biomarker of Gastric Cancer: An Analysis of The Cancer Genome Atlas (TCGA) Data

Abstract

Background:Glutathione peroxidase 8 (GPX8) has previously been shown to play a role in Keshan disease. In the present study, we explored the prognostic relevance of GPX8 expression in patients with gastric cancer (GC) based upon The Cancer Genome Atlas (TCGA) data. Material/Methods:We assessed the relationship between the expression of GPX8 and clinicopathological findings in GC patients via logistic regression analyses, Kruskal-Wallis tests, and Wilcoxon signed-rank tests. We further assessed the prognostic relevance of specific variables using Kaplan-Meier and Cox regression analyses. We lastly conducted gene set enrichment analyses (GSEA). Results:We detected a significant association between elevated GPX8 levels and more advanced GC tumor stage (OR=5.92 for I vs. IV), as well as more advanced T (OR=22.91 for T1 vs. T4) and N classification (OR=1.82 for N0 vs. N3). We found worse prognosis in patients expressing high levels of GPX8 relative to those with lower expression of this gene (P=0.021). In a univariate analysis, we found high GPX8 expression was strongly correlated with worse OS (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.01 -1.08; P=0.018), and multivariate analysis confirmed that GPX8 expression independently predicts GC patient OS (HR: 1.04; CI: 1.00 -1.08, P=0.041). GSEA revealed that elevated GPX8 expression was associated with enrichment of pathways consistent with MAPK signaling, JAK/STAT signaling, TGF-b signaling, melanoma, and basal cell carcinoma. Conclusions:The expression of GPX8 may have prognostic relevance, being positively associated with worse OS in GC patients.

RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

“…To study this issue, we detected the expression of GPX8 in gastric cancer and detected the overexpression of GPX8 in gastric cancer tissues and cell lines. This result was consistent with the previous report that revealed the aberrant high level of GPX8 in gastric cancer tissues compared with normal controls based on TCGA database [ 13 ]. Additionally, our study showed that GPX8 overexpression promoted the proliferation, migration and invasion of gastric cancer cells.…”

“…Zhang et al have analyzed the gastric cancer data in TCGA (the Cancer Genome Atlas) database, found a potential prognostic biomarker- GPX8,and proved the high expression of GPX8 was closely correlated with basal cell carcinoma signaling pathway [ 13 ]. Based on KEGG pathway, Basal cell carcinoma signaling includes the Wnt signaling pathway (Additional file 2 : Figure S1) that is critical for tumorigenesis and development [ 16 ].…”

“…GPX8 as a member of the GPX family plays an important role in protecting cells against oxidative stress [ 11 ]. Moreover, several reports indicated GPX8 dysregulation in gastric cancers through bioinformatics analysis [ 12 , 13 ]. However, the detailed molecular mechanism of GPX8 in gastric cancer has not been reported.…”

“…According to KEGG (Kyoto Gene and Genome Encyclopedia) pathway, Zhang et al used GSEA (Gene set enrichment analysis) to indicate a positive correlation between GPX8 expression and basal cell carcinoma signaling pathway [ 13 ]. Based on the above literature, we clicked the column of “KEGG PATHWAY” in the KEGG website ( https://www.kegg.jp/ ) and entered “basal cell carcinoma signaling pathway” to obtain the pathway information (map05217, Additional file 2 : Figure S1).…”

“…To address this issue, we firstly used bioinformatics methods to identify the potential transcription factors of GPX8 and chose Forkhead box C1 (FOXC1) as an upstream candidate molecule for further analysis. Next, we selected the Wnt signaling pathway as a downstream pathway of GPX8 according to the previous report [ 13 ]. Then, we determined the effects and molecular mechanism of GPX8 in gastric cancer cells using a series of biological experiments.…”