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. Author manuscript; available in PMC: 2022 Feb 2.
Published in final edited form as: Nat Cancer. 2020 Jan 13;1(1):59–74. doi: 10.1038/s43018-019-0010-1

Extended Data Fig. 3 |. Squamous Feature Associated Alteration and Characteristic in Pancreatic Ductal Adenocarcinoma.

Extended Data Fig. 3 |

(a) Entotic CICs in matched glandular (GL) versus squamoid or squamous morphology (SF/SD) in 10 patients. Statistics are performed using Mann-Whitney U test, two-sided. (62, 62,73,38,50,26,33,21,8 and 21 blocks/slides were used for entosis evaluation of PAM02, MPAM06, PAM73, PAM55, PAM22, PAM28, PAM53, PAM80, PAM20 and PAM39). (b) mRNA Expression of squamous markers (TP63, KRT5 and KRT6A) in samples with glandular growth pattern (GL) (n = 133), squamoid features (SF) (n = 18) and squamous differentiation (SD) (n = 63). SF have intermediate expression pattern between SD and GL. Each P-value is calculated by Mann-Whitney U test, two-sided. Lines and bars: median with interquartile range, (c) mRNA expression of TP63, KRT5 and KRT6A. ASC (n = 3) and PDAC with potential SF/SD (n = 9) have higher expression of TP63 than conventional PDAC (n = 133) in TCGA (P = 0.007, MannWhitney U test, two-sided), (d) Keratin network based on mRNA expression. In GL, KRTI9 (normally expressed in ductal epithelia) is a hub in pancreas cancer. In SF, KRT6A and KTR5 (normally expressed in squamous epithelium) have some interaction. In SD, stratified squamous epithelium keratins (KRT4, KRT5, KRTI3, KRTI4) and heavy weight keratins (KRT1 and KRTIO) are expressed in the network, (e)-(g) Tumor purity in PDACs with or without squamous feature, (e) Tumor purity by FACETs in end stage PDAC. Samples with squamous differentiation (SD) (n = 43) have higher tumor purity than samples with squamoid feature (SF) (n = 20) or glandular pattern (GL) (n = 152) (P = 0.012 or P < 0.001, Mann-Whitney U test, two-sided). Lines and bars: median with interquartile range, (f) Intratumoral heterogeneity of tumor purity in end stage PDAC. Samples with SF or SD have higher tumor purity in one tumor (9,11,8,5, 6,11,5,9,4,12, 6,9,21,8,14,8,10,7,11,8,3,7,9, 6 and 8 samples were used for PAM46, MPAM06, PAM54, PAM53, PAM32, PAM02, PAM28, PAM22, PAM16, PAM55, PAM20, PAM39, PAM52, PAM48, PAM24, PAM56, PAM51, PAM49, PAM03, PAM29, PAM25, PAM47, PAM50, PAM27, and PAM04) (g) Absolute tumor purity in TCGA cohort. Absolute tumor purity is not different between conventional PDAC (n = 132) and PDAC with potential SF/SD (n = 9) and ASC (n = 3) (P = 0.601, Mann-Whitney U test, two-sided).