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. 2022 Sep 8;21:178. doi: 10.1186/s12943-022-01646-1

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© The Author(s) 2022

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Integrin beta 4 (ITGB4) expression in HNSCC. A Pathway activities were inferred in HPV-negative TCGA-HNSCC samples using PROGENy (n = 240). Spearman correlations and p-values of the 5-gene signature with pathway activities are depicted. * ≤ 0.05; ** ≤ 0.01; *** ≤ 0.001. B Scatter plots of ITGB4 correlations with EGFR and MAPK pathways in HPV-negative HNSCC of TCGA patients (n = 240) are shown with Spearman correlation and p-value. C ITGB4-correlated genes were subjected to a GSEA using MSigDB hallmark gene sets. Top 15 regulated hallmarks are depicted with gene counts and adjusted p-values. D ITGB4 expression was compared in matched pairs of normal mucosa and HPV-negative HNSCCs of TCGA (n = 34). Matched expression values are shown in a box plot whiskers graph (t-test **** ≤ 0.0001). E Representative examples of ITGB4 expression in normal mucosa (n = 64), primary tumor (n = 80) belonging to n = 84 patients, and in triplets including lymph node metastases (n = 26) from HPV-neg. and -pos. HNSCC of the LMU cohort. F-G IHC scoring of ITGB4 protein expression is shown in scatter dot plots with means and SD for all samples and stratified according to HPV-status. Ns: not significant, **** ≤ 0.0001 (t-test and One-way ANOVA). H Representative examples of ITGB4 and laminin 5 expression in consecutive sections of normal mucosa and HNSCC are shown. I Double immunofluorescence staining of ITGB4 (red), laminin 5 (green), and DAPI (blue) in HNSCC with edge-localized (left) or homogeneous ITGB4 expression (right)