Identification of cuproptosis-related genes in septic shock based on bioinformatic analysis

Abstract

Background: Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear.

Methods: The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed.

Results: SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups.

Conclusion: This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

Fig 1. Screening of cuproptosis-related genes related to septic shock progression.

(A) The volcano plot and (B) heat map displayed the DEGs between control and septic shock groups. Blue, downregulated genes; Red, upregulated genes. (C) The overlapping genes between 19 cuproptosis-related genes and DEGs were screened using the Venn map.

Fig 2. The diagnostic value of hub genes in predicting septic shock.

(A) The Box plots displayed SLC31A1, MTF1, LIAS and LIPT1 levels between control and septic shock groups in the GSE26640 cohort. (B) The Box plots displayed SLC31A1, MTF1, LIAS and LIPT1 levels between control and septic shock groups in the GSE33118 cohort. (C) ROC curves verified the diagnostic value of SLC31A1, MTF1, LIAS and LIPT1 genes in the GSE26640 cohort. (D) ROC curves verified the diagnostic value of SLC31A1, MTF1, LIAS and LIPT1 genes in the GSE33118 cohort. (E) RT-qPCR analysis of SLC31A1, MTF1, LIAS and LIPT1 levels in peripheral blood lymphocytes from healthy controls and patients with septic shock. *P<0.05, **P<0.01, ***P<0.001.

Fig 3. GO and KEGG enrichment analyses of hub genes in septic shock.

(A) Top 10 KEGG enrichment pathways, (B) top 10 GO-BP terms, (C) top 10 GO-CC terms and (D) top 10 GO-MF terms of the DEGs between high-SLC31A1, -MTF1, -LIAS or -LIPT1 level group and low-SLC31A1, -MTF1, -LIAS or -LIPT1 level group respectively.

Fig 4. GSEA and GSVA analyses of hub genes in septic shock.

(A, B, C, D) GSEA results between high-SLC31A1, -MTF1, -LIAS or -LIPT1 level group and low-SLC31A1, -MTF1, -LIAS or -LIPT1 level group respectively. (E, F, G, H) GSVA results between high-SLC31A1, -MTF1, -LIAS or -LIPT1 level group and low-SLC31A1, -MTF1, -LIAS or -LIPT1 level group respectively.

Fig 5. Evaluation of immune infiltration between control and septic shock samples.

(A) Bar plot displayed the proportions of the 22 types of infiltrated immune cells in each sample. (B) The Box plots displayed the proportions of 22 immune cells between control and septic shock groups. (C) The correlation between SLC31A1, MTF1, LIAS or LIPT1 level and immune cells.

Fig 6. Construction of hub gene-miRNAs-lncRNAs network.

(A) The volcano plot displayed the differential expressed lncRNAs between control and septic shock groups in the GSE57065 cohort. (B) The volcano plot displayed the differential expressed miRNAs between control and septic shock groups in the GSE57065 cohort. (C) The network constructed by SLC31A1 gene with 3 miRNAs and top 15 lncRNAs. (D, E, F) The networks constructed by MTF1, LIAS or LIPT1 gene with top 15 miRNAs and top 15 lncRNAs.

Fig 7. Construction of hub gene-TFs network.

(A) The network constructed by SLC31A1 gene with 4 TFs. (B, C, D) The networks constructed by MTF1, LIAS or LIPT1 gene with top 15 TFs.