Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 28;102(30):e34230.
doi: 10.1097/MD.0000000000034230.

A cuproptosis-related gene signature and associated regulatory axis in stomach adenocarcinoma based on bioinformatics analysis

Dongxiao Ding  1   2 , Dianqian Wang  1 , Yunsheng Qin  3   4
Affiliations

A cuproptosis-related gene signature and associated regulatory axis in stomach adenocarcinoma based on bioinformatics analysis

Dongxiao Ding et al. Medicine (Baltimore). .

Abstract

Stomach adenocarcinoma (STAD) is a highly aggressive and extremely heterogeneous gastric cancer characterized by high morbidity and mortality. Cuproptosis, a copper (Cu)-triggered modality of mitochondrial cell death, could regulate tumor proliferation and metastasis. Least absolute shrinkage and selection operator cox regression analysis was constructed to develop a prognostic cuproptosis-related signature. A lncRNA-miRNA-mRNA regulatory axis was performed to explore cuproptosis-related mechanism for STAD. The expression of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A was upregulated in STAD versus normal tissue. We also summarized single nucleotide variants and copy number variation landscape of cuproptosis-related gene in STAD. Further analysis demonstrated that STAD patients with high expression of CDKN2A, DLD, GLS, and MTF1 and low expression of DLAT, FDX1, PDHA1 and PDHB had a poor overall survival (OS) and post progression survival (PPS) rate. By performing least absolute shrinkage and selection operator cox regression analysis, we constructed a cuproptosis-related prognostic signature for STAD. Further analysis demonstrated a significant correlation between FDX1 expression and immune cell infiltration, tumor mutational burden (TMB) score, microsatellite instability (MSI) score and drug sensitivity. Univariate and multivariate analysis indicated FDX1 expression and clinical stage as independent factors affecting the prognosis of STAD patients. We also identified a lncRNA MALAT1/miR-328-3p/FDX1 regulatory axis for STAD. Multi-omics approaches were performed to develop a cuproptosis-related signature with 2 genes (FDX1 and MTF1) for STAD. We also identified a lncRNA MALAT1/miR-328-3p/FDX1 regulatory axis for STAD.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
The expression, CNV and SNV landscape of cuproptosis-related genes in STAD. (A) The mRNA level of cuproptosis-related gene in STAD versus normal tissues in TCGA STAD dataset. (B and C) SNV landscape of cuproptosis-related gene in STAD. (D) CNV landscape of cuproptosis-related gene in STAD. *P < .05; **P < .01; ***P < .001; -P > .05. CNV = copy number variation, STAD = stomach adenocarcinoma, SNV = single nucleotide variants, TCGA = The Cancer Genome Atlas.
Figure 2.
Figure 2.
The enriched items in functional enrichment analysis. (A) The enriched items in gene ontology analysis. (B) The enriched items in Kyoto Encyclopedia of Genes and Genomes pathways analysis. BP = biological process, CC = cellular component, MF = molecular function.
Figure 3.
Figure 3.
The prognostic significance of cuproptosis-related genes in STAD. (A) The overall survival curve in STAD patients with high and low expression of cuproptosis-related genes. (B) The recurrence-free survival curve in STAD patients with high and low expression of cuproptosis-related genes. STAD = stomach adenocarcinoma.
Figure 4.
Figure 4.
Cuproptosis-related prognostic signature for STAD in TCGA cohort. (A and B) The coefficient and partial likelihood deviance of prognostic signature. (C) The riskscore distribution, patient survival status and gene expression profile of prognostic signature. (D and E) The survival curve of STAD patients with high/low riskscore and ROC curve of prognostic signature. STAD = stomach adenocarcinoma, TCGA = The Cancer Genome Atlas.
Figure 5.
Figure 5.
Cuproptosis-related prognostic signature for STAD in ICGC cohort. (A and B) The coefficient and partial likelihood deviance of prognostic signature. (C) The riskscore distribution, patient survival status and gene expression profile of prognostic signature. (D and E) The survival curve of STAD patients with high/low riskscore and ROC curve of prognostic signature. ICGC = International Cancer Genome Consortium, STAD = stomach adenocarcinoma.
Figure 6.
Figure 6.
Immune cell infiltration, TMB, MSI and drug sensitivity analysis of FDX1/MTF1 in STAD. (A-B) Correlation between the expression of FDX1 and MTF1 and the abundance of immune cell in STAD. (C-D) Correlation between CNV of FDX1 and MTF1 and immune cell infiltration in STAD. (E-F) Correlation between FDX1expression and TMB/MSI score in STAD. (G-H) Correlation between MTF1 expression and TMB/MSI score in STAD. (I) Correlation between MTF1 expression and drug sensitivity in STAD. MSI = microsatellite instability, STAD = stomach adenocarcinoma, TMB = tumor mutational burden.
Figure 7.
Figure 7.
lncRNA-miRNA-mRNA regulatory axis in STAD. (A) The miRNA targets predicted by miRDB, miRWalk, and StarBase. (B and C) The expression and prognosis value of miR-328-3p in STAD. (D) The lncRNA targets predicted by lncBase and StarBase. (E and F) The expression of NEAT1 and MALAT1 in STAD. (G) The prognosis significance of MALAT1 in STAD. STAD = stomach adenocarcinoma.
See this image and copyright information in PMC

References

    1. Luo L, Li L, Liu L, et al. . A necroptosis-related lncRNA-based signature to predict prognosis and probe molecular characteristics of stomach adenocarcinoma. Front Genet. 2022;13. - PMC - PubMed
    1. Sung H, Ferlay J, Siegel RL, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. - PubMed
    1. He Y, Zhang H, Zhang Y, et al. . Comprehensive characterization of transforming growth factor beta receptor 1 in stomach adenocarcinoma identifies a prognostic signature for predicting clinical outcomes and immune infiltrates. Int J Gen Med. 2022;15:3375–91. - PMC - PubMed
    1. Zhang L, Song X, Chen X, et al. . Circular RNA CircCACTIN promotes gastric cancer progression by sponging MiR-331-3p and regulating TGFBR1 expression. Int J Biol Sci. 2019;15:1091–103. - PMC - PubMed
    1. Tsvetkov P, Coy S, Petrova B, et al. . Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375:1254–61. - PMC - PubMed