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. 2023 Apr 24;14:2353. doi: 10.1038/s41467-023-38064-w

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A GSEA of data set published in Cao et al.²³ (matched tumor and adjacent tissue samples. n = 21) on “Gene ontology for Hyaluronic Acid binding”. Leading edge genes significantly deregulated are marked with red star. B HAPLN1 expression levels in normal adjacent or PDAC tumor tissue according to TNMplot, (Normal: Min = 0, Q1 = 0, Med = 0, Q3 = 0, Max = 5, Upper Whisker = 0, n = 252; Tumor: Min = 0, Q1 = 7, Med = 19, Q3 = 57, Max = 1960, Upper Whisker = 129, n = 177). Unpaired non-parametric Mann–Whitney two-tailed U test was applied. C–E GSEA on data set of Cao et al. (2021). Before analysis PDAC patients were divided in HAPLN1 high/low according to mean HAPLN1 expression. Gene sets of “Basal subtype” (C), “Classical subtype” (D) or “Hallmark of Epithelial-to-Mesenchymal transition” (E). n = 140. F Overall survival (OS) of PDAC patients stratified in two cohorts according to their mean HAPLN1 mRNA (n = 135) or protein expression levels (n = 125). For OS log-rank (Mantel–Cox) test was applied. G Human PDAC and adjacent tissue samples were sorted for epithelial/tumoral cells (EpCAM⁺ CD45⁻), immune cells (EpCAM⁻ CD45⁺) and stromal cells (EpCAM⁻ CD45⁻). HAPLN1 expression in cell types isolated from tumor by RNAseq; expression normalized to control tissue. Epithelial: Normal, Min = 0,7140, Q1 = 0,7140, Med = 0,7140, Q3 = 0,7140, Max = 0,7140, Upper Whisker = 0, n = 7; Tumor, Min = 0,7140, Q1 = 0,7140, Med = 0,7140, Q3 = 2,520, Max = 6,651, Upper Whisker = 1,746, n = 31. Immune: Normal, Min = 0,7140, Q1 = 0,7140, Med = 0,7140, Q3 = 2,511, Max = 3,343, Upper Whisker = 1,147, n = 5, Tumor, Min = 0,7140, Q1 = 0,7140, Med = 0,7140, Q3 = 2,623, Max = 4,765, Upper Whisker = 1,363, n = 26; Stromal: Normal, Min = 0,7140, Q1 = 0,7140, Med = 2,868, Q3 = 5,211, Max = 7,117, Upper Whisker = 2,622 n = 5; Tumor, Min = 0,7140, Q1 = 4,567, Med = 5,332, Q3 = 6,618, Max = 7,474, Upper Whisker = 2,001, n = 9. Dots represent biological replicates. Unpaired non-parametric Mann–Whitney two-tailed U test was applied. H HAPLN1 protein staining in human PDAC patient samples (n = 20) show staining in areas with tumoral cells. Three examples shown. Scale bar: 100 µm, zoom 25 µm.