Fig. 5

GSEA analysis showing significant enrichment of genes progressively adapted to the sustained acidic pHe stress. a Table showing six significant functional classes and pathways identified in SUIT-2 PDAC cells progressively adapted to acidotic pHe stress. The normalized enrichment scores (NES), p-values, and false discovery rates (FDR) obtained from the comparison results of the L.A. vs S.A. cell group; the L.A. vs Buff cell group; and the S.A. vs Buff cell group were listed. b Enrichment score (ES, green color) plots of GSEA-extracted representative pathways from microarray data. Six functional pathways were markedly enriched upon tumor cell adaptation to sustained acidic pHe stress (see comparisons of the L.A. vs S.A. group; the L.A. vs Buff group; and the S.A. vs Buff group). The gene sets of six functional categories were ranked according to the NES and FDR values. Negative and positive ES values point to gene sets over-represented in the topmost down-regulated or up-regulated genes in acid-adapted cells. Vertical black bars in lower areas refer to individual genes in a functional category, and their position reflects the contribution of each gene from the Human Transcriptome Array 2.0 to the ES. Genes that belong to the leading-edge subset (i.e., genes that appear at or after the ES minimum and at or before the ES maximum) contribute to the enrichment signal. c-h Heatmaps represent differential expression of genes belonging to the leading-edge subset of the indicated functional categories. i Kaplan-Meier survival analysis of 19 genes identified in the leading edge of the six aforementioned functional categories. The mRNA expression levels were significantly related to PDAC patient survivals in TCGA-PAAD cohort data. All p-values correspond to the log-rank test comparing the survival curves