Gene Expression Comparison between the Lymph Node-Positive and -Negative Reveals a Peculiar Immune Microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study
Abstract
:1. Introduction
2. Results
2.1. Gene Expression Analysis Comparing PDAC Patient-Derived Specimen Identified a Characteristic Biological Signature Depending on Lymph Node Status
2.2. Biological Network and Gene Set Enrichment Analysis of Database of Essential Genes
2.3. In Silico Microenvironmental Composition Estimation
2.4. WNT Inhibition Enhances Pancreatic Cancer Cell Immune-Mediated Killing In Vitro
2.4.1. XAV-939 Restrains PDAC Cells Tumor Functions, Exerts Cytotoxic Effect, and Halts Cancer-Migration Potential
2.4.2. XAV-939 Induced Modulation of β-catenin Expression
2.4.3. XAV-939 Enhances Immune Cell-Dependent PDAC Cell Killing
2.4.4. XAV-939 Modulates CD40 Expression in mDCs upon PDAC Cell Co-Culture
2.5. Effect of XAV-939 on Short-Term Culture of PDAC Cells Cancer-Related Protein Profile
3. Discussion
4. Material and Methods
4.1. Dataset
4.2. Differential Gene Expression Analysis, GO Enrichment, and Biological Network
4.3. In silico Estimation of Microenvironmental Cell Types
4.4. Cell Culture
4.5. β-Catenin Expression by Real-Time PCR
4.6. Cytoxicity Assay
4.7. Killing Assay
4.8. CD40 Expression in mDC
4.9. Migration Test by Wound Healing (Scratch) Assay
4.10. Invasion Assay
4.11. Western Blotting Analysis
4.12. Proteome Profiler Antibodies Array
4.13. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Argentiero, A.; De Summa, S.; Di Fonte, R.; Iacobazzi, R.M.; Porcelli, L.; Da Vià, M.; Brunetti, O.; Azzariti, A.; Silvestris, N.; Solimando, A.G. Gene Expression Comparison between the Lymph Node-Positive and -Negative Reveals a Peculiar Immune Microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study. Cancers 2019, 11, 942. https://doi.org/10.3390/cancers11070942
Argentiero A, De Summa S, Di Fonte R, Iacobazzi RM, Porcelli L, Da Vià M, Brunetti O, Azzariti A, Silvestris N, Solimando AG. Gene Expression Comparison between the Lymph Node-Positive and -Negative Reveals a Peculiar Immune Microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study. Cancers. 2019; 11(7):942. https://doi.org/10.3390/cancers11070942
Chicago/Turabian StyleArgentiero, Antonella, Simona De Summa, Roberta Di Fonte, Rosa Maria Iacobazzi, Letizia Porcelli, Matteo Da Vià, Oronzo Brunetti, Amalia Azzariti, Nicola Silvestris, and Antonio Giovanni Solimando. 2019. "Gene Expression Comparison between the Lymph Node-Positive and -Negative Reveals a Peculiar Immune Microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study" Cancers 11, no. 7: 942. https://doi.org/10.3390/cancers11070942