Fig 2: Glucose-6-phosphate isomerase (GPI) functional clustering and interaction network analysis of GPI-related genes. (A) Heatmap showing the top 50 genes in lung adenocarcinoma (LUAD) that were positively and negatively related to GPI. Red represents positively related genes and blue represents negatively related genes. (B) Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of GPI-related genes in LUAD. (C) Venn diagram of the GPI-related genes and the survival-related and upregulated genes in LUAD. (D) GO term and KEGG pathway analyses of the GPI-related genes and LUAD survival-related genes in LUAD.

Fig 3: Correlation analysis between glucose-6-phosphate isomerase (GPI) expression and immunoinhibitors and immunostimulators. (A) Correlation between GPI and immunoinhibitors in tumors by heatmap analysis. (B) Correlation between GPI and immunostimulators in tumors by heatmap analysis. (C–E) GPI expression is negatively correlated with the immunostimulators CD40L, IL6R, and TMEM173 in lung adenocarcinoma (LUAD).

Fig 4: Correlation analysis of glucose-6-phosphate isomerase (GPI) expression and immune infiltration in lung adenocarcinoma (LUAD). (A, B) Differential distribution of immune cells in patients with high GPI expression and low GPI expression. (C–N) Correlation between the expression level of GPI and immune infiltration in lung adenocarcinoma (LUAD): (C) Th2 cells, (D) regulatory T cells, (E) gamma delta T cells, (F) NK CD56bright cells, (G) dendritic cells (DC), (H) immature DC, (I) Mast cells, (J) central memory T cells, (K) Macrophages, (L) Eosinophils, (M) effective memory T cell, (N) CD8+ T cells. *p < 0.05, **p < 0.01, ***p < 0.001, ns, no significance.

Fig 5: Low villous SDHB expression reduces succinate accumulation and correlates with RSA.a Western blot analysis of glycolysis and citrate cycle enzymes in villi from individuals with RSA or normal controls (n = 6 persons/group). Right panel: quantitative western blot results of six samples per group. b mRNA expression of glycolytic and citrate cycle genes in villi from individuals with RSA and normal controls (n = 6 persons/group). Exact P values in b are listed below: HK1 0.800, GPI 0.326, TPI 0.369, PGK1 0.202, ENO1 0.145, PKM2 0.685, 6PGD 0.715, TKT 0.914, PDHA1 0.691, CS 0.841, IDH1 0.546, IDH2 0.801, IDH3A 0.969, OGDH 0.163, SUCLA2 0.816, SDHA 0.00134, SDHB 0.00243, SDHC 0.000233, FH 0.222, and MDH2 0.938. c Relative SDH activities in SDHB-overexpressing JEG3 and HTR8 cells and control cells (n = 5 independent experiments). The SDHB overexpression efficiency is shown in the right panel. d Succinate levels in SDHB-overexpressing JEG3 and HTR8 cells and control cells (n = 5 independent experiments). e Relative SDH activities in SDHB-knockdown JEG3 and HTR8 cells and control cells (n = 5 independent experiments). The SDHB-knockdown efficiency is shown in the right panel. f Succinate levels in SDHB-knockdown JEG3 and HTR8 cells and control cells (n = 5 independent experiments). g The relative SDH activities in villi and decidua tissues from both RSA patients and normal controls (n = 10 persons/group). a–g Data represent the mean ± standard error; ns not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ns not significant. Two-tailed unpaired Student’s t tests in a–g. Source data are provided as a Source Data file.