Fig. 6: Lineage-specific early PDAC model reveals candidates for diagnostic markers.

a Expression of 140 genes which were significantly overexpressed in acinar-KPTS cells compared with fresh ductal, fresh acinar, and acinar metaplastic cells (fold change >4, adj. p < 0.05, by negative binomial Wald test using DESeq2 1.36.0 in R software). The middle line of box represents the median value, the bounds of box represent the IQR, and the whiskers extend to 1.5 × IQR. b Expression of 696 genes which were significantly overexpressed in ductal-KPTS cells compared with fresh ductal, fresh acinar, and acinar metaplastic cells (fold change >4, adj. p < 0.05, by negative binomial Wald test using DESeq2). The middle line of box represents the median value, the bounds of box represent the IQR, and the whiskers extend to 1.5 × IQR. c Venn diagram of the intersections of 140 acinar-KPTS high genes, 696 ductal-KPTS high genes, and 2805 TCGA high genes. The 2805 TCGA high genes were identified by comparing TCGA PDAC samples with the GTEx normal pancreas dataset (fold change >4, adj. p < 0.05, by negative binomial Wald test using DESeq2). d Annotation of 51 overlapped genes identified in (c). e Expression of selected genes in our samples (fresh ductal n = 5, fresh acinar n = 5, acinar-metaplastic n = 11, acinar-KPTS n = 3, ductal-KPTS n = 4) as well as GTEx pancreas (n = 328) and TCGA PDAC samples (n = 149). The middle line of box represents the median value, the bounds of box represent the IQR, and the whiskers extend to 1.5 × IQR. f–g Immunohistochemistry staining of AHNAK2 (f) and AREG (g) proteins in the KPTS tumors generated in this work (n = 2 with 8 field of views for each), and a human pancreatic cystic neoplasm sample as well as adjacent normal pancreas (8 field of views for each). Scale bar: 25 µm. h–i Representative immunohistochemistry staining of AHNAK2 (h) and AREG (i) proteins in a human PDAC array including both tumor and adjacent normal pancreas from 28 PDAC patients (2 tumor tissues and 1 adjacent normal tissue per patient). Scale bar: 50 µm. Pearson’s Chi-squared test with Yates’ continuity correction was used to assess the statistical significance of the number of positive staining between tumor tissues versus normal tissues.