Characterizing the intra-tumor heterogeneity and its association with lymph node metastasis (LNM). (IMAGE)
Caption
(A) Pancreatic ductal adenocarcinoma cells were integrated with public datasets and re-clustered with unsupervised clustering. (B) Bar plot of the proportion of subclusters in LNM and non-LNM groups. (C) S100A2 was specifically expressed in cluster 0. (D) S100A2 was specifically expressed in the LNM group. (E) The survival plot showed the association of S100A2 with worse overall survival in the TCGA PAAD dataset (p value: log-rank test). (F) Representative images of immunohistochemistry staining in primary tumor samples with different LNM status and lymph node samples with LNM and the box plot of H-scores calculated for each sample using five representative fields. (G) Wound healing assay showed decreased migratory capability after knockdown of S100A2 using two distinct shRNAs and increased migratory capability after overexpression of S100A2 (p value: Welch's t-test after Shapiro–Wilk normality test for statistical analysis). (H) Transwell migratory assay showed decreased migratory capability after knockdown of S100A2 using two distinct shRNAs and increased migratory capability after overexpression of S100A2 (p value: Welch's t-test was used after Shapiro–Wilk normality test for statistical analysis). (I) In vivo imaging and bar plot showed a larger tumor burden determined by bioluminescence imaging in a hemi-spleen injection model of liver metastasis (p value: Welch's t-test after Shapiro–Wilk normality test for statistical analysis). (J) The survival plot showed worse overall survival after overexpression of S100A2 in KPC1199 (p value: log-rank test). (K) Dot plot of the enrichment of multiple pathways in down-regulated genes after S100A2 knockdown in AsPC-1 using Metascape. (L) Heatmap of down-regulated genes associated with epithelial–mesenchymal transition, cell motility, and cell cycles after S100A2 knockdown. (M) Gene set enrichment analysis (GSEA) showed the enrichment of Gruetzmann pancreatic cancer up gene signature in down-regulated genes after S100A2 knockdown.
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Genes & Diseases
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