Fig 1: Comparison of plasma protein concentrations between mining region residents (MRR) and non-mining region residents (NMR). Box plots show that plasma levels of NFKB1 (A) and CDKN2A (B) were significantly higher in the MRR group compared to the NMR group. No significant group differences were observed for IGF2 (C)and APOA5 (D).
Fig 2: Expression of apoptosis-related genes in GC and HCs. (A) Heatmap of the Spearman’s rank correlation analysis between 8 genera and 30 significant pathways in GC. (B) Heatmap of the Spearman’s rank correlation analysis between 8 genera and 63 significant orthologs in GC. (C) Correlation analysis between 3 genera (columns) and 4 functional profiles (Ko04215-apoptosis, K07190-phosphorylase kinase alpha/beta subunit, K12767-serine/threonine-protein kinase, K08291-G protein-coupled receptor kinase) in GC and HCs. Full pathway and ortholog names are provided in Table S8. (D–I) Plasma level of (D) IL-6, (E) STAT3, (F) TGF-β, (G) NF-kB, (H) p-Smad2, and (I) p-Smad3 from 16 samples selected based on age and sex variance in each group. (J) Correlation analysis between 3 genera (columns) and 6 target molecules (rows) in GC and HCs. *p < 0.05, **p < 0.01, and ***p < 0.001. PKA; phosphorylase kinase alpha/beta subunit, AKT; protein kinase B, GRK; G protein-coupled receptor kinases, IL-6; Interleukin-6, STAT3; Signal transducer and activator of transcription 3, TGF-β1; Transforming growth factor beta 1, NF-κB; Nuclear factor kappa-light-chain-enhancer of activated B cells. All p-values were adjusted for multiple comparisons using the Benjamini–Hochberg FDR correction.
Fig 3: Added-variable (AV) plots showing significant associations between DNA methylation, mRNA expression, metal exposure, and plasma protein levels for NFKB1 (A–C) and IGF2 (D–G). All numeric point labels automatically generated by the avPlot() function have been removed for clarity. All AV plots are based on the combined dataset (MRR + NMR), and each panel now includes explicit labeling to indicate whether the comparison involves MRR, NMR, or both (A–B) NFKB1 protein levels were significantly associated with DNA methylation levels at chr4:102501416 (A) and chr4:102501517 (B). (C) NFKB1 protein levels were higher in mining region residents (MRR). (D) IGF2 protein levels were positively associated with its transcript expression and (E) positively associated with the cumulative Z-score of essential metal concentrations. (F–G) IGF2 protein levels were higher in males (F) and positively associated with age (G).
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