Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: ITGAV and ITGB3 are overexpressed in pancreatic cancer and are associated with poor patient prognosis. ( A – B ) Box plots showing the mRNA expression levels of ITGAV ( A ) and ITGB3 ( B ) in Pancreatic tumor tissues (T, n = 179) compared to normal pancreatic tissues (N, n = 171), retrieved from the TCGA database via GEPIA2. Both genes are upregulated in tumor tissues (red boxes) compared to normal (gray boxes); p < 0.05.(C–D) Kaplan–Meier survival analyses from the UALCAN database demonstrating that high expression of ITGAV ( C ) is significantly associated with reduced overall survival in PAAD patients ( p = 0.031), while high ITGB3 expression ( D ) shows a non-significant trend toward poor survival ( p = 0.065). (E–F) DNA methylation heatmaps for ITGAV ( E ) and ITGB3 ( F ) illustrating CpG site-specific methylation differences between normal and tumor pancreatic tissues. Tumor samples exhibit increased promoter methylation, particularly in gene regions showing upregulated expression, indicating altered methylation-associated regulation

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Expressing, DNA Methylation Assay, Methylation

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Single-cell transcriptomic mapping of ITGAV and ITGB3 expression in PAAD tissues. ( A ) UMAP visualization of major cellular lineages in human Pancreatic tumor single-cell datasets ( GSE162708 ), including malignant ductal cells, fibroblasts, endothelial cells, B/T/NK lymphocytes, and myeloid populations. ( B – C ) Expression distribution of ITGAV and ITGB3 across all major cell clusters reveals enrichment in malignant and fibroblast compartments.( D – G ) Subset analyses of ITGAV expression across metastatic, normal, PBMC, and primary tumor samples demonstrate strong induction in metastatic (37.01%) and tumor clusters (30.29%) compared with normal (3.65%) and PBMC (2.87%) populations. ( H – K ) Corresponding ITGB3 expression maps show restricted but distinct localization, predominantly within metastatic and tumor epithelial clusters, with negligible expression in normal or PBMC samples

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Single Cell, Expressing

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Cell-type-specific and malignancy-associated expression of ITGAV and ITGB3 in single-cell PAAD datasets. ( A – B ) Violin plots showing differential expression of ITGAV ( A ) and ITGB3 ( B ) across major cellular lineages (B cells, CD8⁺ T cells, endothelial cells, fibroblasts, malignant epithelial cells, mast cells, macrophages/monocytes, myofibroblasts, and NK cells) from normal, PBMC, tumor, and metastatic pancreatic tissues. ITGAV shows highest expression in malignant, macrophage, and myofibroblast populations, while ITGB3 is preferentially enriched in myofibroblasts and macrophage-like stromal compartments. Statistical significance: p < 0.05 (*), p < 0.01 (**), ** p < 0.0001; ns, not significant. ( C – D ) Violin plots regrouped by functional category (immune, stromal, and malignant compartments) further highlight selective enrichment of ITGAV in stromal and malignant cell clusters, with comparatively lower expression of ITGB3, suggesting complementary but nonredundant roles of integrin αvβ3 subunits in tumor–stroma crosstalk

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Expressing, Single Cell, Quantitative Proteomics, Functional Assay

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Gene set enrichment analysis (GSEA) of ITGAV and ITGB3-associated transcriptomes in pancreatic cancer. ( A ) GSEA of ITGAV-high vs. ITGAV-low expression groups revealed significant enrichment of hallmark gene sets related to glycolysis, apoptosis, epithelial–mesenchymal transition (EMT), inflammatory response, KRAS signaling, and hypoxia. Representative enrichment plots highlight apoptosis and EMT pathways. ( B ) GSEA of ITGB3-high vs. ITGB3-low expression groups demonstrated enrichment in hallmark gene sets including TNFα signaling via NF-κB, apoptosis, EMT, KRAS signaling, inflammatory response, and angiogenesis. Representative enrichment plots show EMT and apoptosis pathways. Together, these findings suggest that ITGAV and ITGB3 converge on shared oncogenic programs that promote tumor progression and resistance mechanisms in pancreatic cancer

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Expressing

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Immunohistochemical and immunofluorescent validation of ITGAV and ITGB3 expression in pancreatic cancer tissues and model cells. ( A – C ) Representative IHC images from the Human Protein Atlas showing ITGAV (antibody: HPA004856) and ITGB3 (antibody: HPA028463) staining in normal pancreas and PAAD tissues. Normal exocrine glandular cells exhibit weak or undetectable ITGAV staining, whereas tumor cells display strong cytoplasmic and membranous expression (> 75% of cells). ITGB3 shows moderate staining intensity localized to tumor cell membranes, with minimal signal in normal tissue.( D – E ) Bar charts summarize staining intensity across all available samples ITGAV ( n = 12) and ITGB3 ( n = 10) indicating that high to Low expression levels dominate in tumor tissues, while normal counterparts remain largely negative

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Immunohistochemical staining, Biomarker Discovery, Expressing, Staining

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Protein–protein interaction network and correlation of ITGAV and ITGB3 with EGFR expression.( A ) Protein–protein interaction (PPI) network of ITGAV and ITGB3 and their associated genes, generated using the STRING database. The network illustrates key predicted interactions involved in cell adhesion, migration, and epithelial–mesenchymal transition (EMT). Table listing interaction scores between ITGAV/ITGB3 and selected partner genes, highlighting strong associations with EGFR (interaction score > 0.6 for both). ( B–C ) Correlation analysis using GEPIA shows a significant positive correlation between EGFR expression and ITGAV ( B ) as well as EGFR and ITGB3 ( C ) in PAAD samples. Spearman correlation coefficients and p-values are indicated, supporting a functional association between integrin αvβ3 subunits and EGFR signaling in pancreatic cancer

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Expressing, Generated, Migration, Functional Assay

Journal: Journal of Translational Medicine

Article Title: Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma

doi: 10.1186/s12967-026-07865-0

Figure Lengend Snippet: Pathway enrichment analysis of ITGB3-associated genes highlights EMT, fibroblast activation, and EGFR pathway crosstalk. Bar plot shows the top 10 enriched biological pathways associated with ITGB3 expression in TCGA-PAAD. Significance is represented as -log(p-value) on the x-axis. ITGB3-associated genes are enriched in EMT, ECM remodeling, and TGF-β-driven fibroblast migration pathways that contribute to desmoplasia and metastasis. Enriched pathways related to stellate cell activation, cytoskeleton reorganization, and tumor–stroma signaling also align with EGFR-linked oncogenic processes, indicating integrin–EGFR pathway synergy within the pancreatic tumor microenvironment

Article Snippet: IHC images from the Human Protein Atlas revealed that both ITGAV (antibody HPA004856) and ITGB3 (antibody HPA028463) are markedly upregulated in PDAC tissues compared with the normal pancreas.

Techniques: Activation Assay, Expressing, Migration