Fig. 3: 4q loss induced fatty acid metabolism disruption promotes cell proliferation.

a Forest plot showed the hazard ratios of the significant arm events (q value < 0.1), p values were listed on the right. b Comparison between the 4q loss group and the WT group. Top panel, selection of significantly different expressed genes (FC > 1.5, p < 0.05) at both the mRNA and protein levels. Middle panel, pathways enriched by genes that upregulated proteins and mRNAs in 4q loss group. Bottom panel, pathways enriched by genes that downregulated proteins and mRNAs in 4q loss group. c Heatmap of the GSVA scores of pathways enriched by differentially expressed genes in b. d Screening of the cis gene on chromosome 4q. Top panel, selection of candidate cis genes on 4q according to expression level in the 4q loss group compared with WT group and correlation with the overall survival. Bottom panel, heatmap showing the HADH copy number, protein expression, and mRNA abundance. e Kaplan–Meier curves for overall survival based on the protein expression of HADH (log-rank test, p = 0.011). f The scatter plot showed the correlations between GSVA scores of the KEGG pathways and the expression of HADH at both proteins and mRNA levels. The x-axis represented the Spearman’s correlations at the protein level, and the y-axis represented the Spearman’s correlations at mRNA level. Positive correlates were colored pink, and negative correlates were colored blue (Spearman’s p value < 0.05). g Schematic diagram of the comparison between the 4q loss group and the WT group of fatty acid metabolism pathway in AMPAC. h Heatmap of MS-based 191 fatty acyls in SNU-478 cells and the pathway enrichment of the 191 metabolites were shown on the right. i Heatmap of MS-based 130 fatty acyls in SNU-869 cells and the pathway enrichment of the 130 metabolites were shown on the right. j Bar plot illustrated the abundance of palmitaldehyde in the control, empty vector, and HADH-KD groups in SNU-478 according to the MS-based untargeted metabolomics result (two-way ANOVA test). k Bar plot illustrated the abundance of palmitic acid in the control, empty vector, and HADH-KD groups in SNU-869 according to the MS-based untargeted metabolomics result (two-way ANOVA test). l The scatter plot described the correlation between HADH protein expression and the GSVA score of the PI3K-AKT pathway (Spearman’s r = 0.32, p < 1e−4). m The violin plot of the GSVA score of Hallmark PI3K-AKT pathway in the control group and HADH-KD group in SNU-478 (Student’s t-test, p < 0.05). n The violin plot of the GSVA score of Hallmark PI3K-AKT pathway in the control group and HADH-KD group in SNU-869 (Student’s t-test, p < 0.05). o Proliferation of SNU-478 cells associated with various treatments (n = 5, mean ± SEM, two-sided Student’s t-test). p Proliferation of SNU-869 cells associated with various treatments (n = 3, mean ± SEM, two-sided Student’s t-test). q Xenograft tumor volumes of HADH-KD groups and empty vector groups (SNU-478). r Xenograft tumor images of the SNU-478 cells subcutaneously injected into nude mice. s The systematic diagram summarized the impact of dysregulation of fatty acid metabolism due to the 4q loss promotes cell proliferation.