Calcium electroporation of esophageal cancer induces gene expression changes: a sub-study of a phase I clinical trial.

Charlotte Egeland, Lukas Balsevicius, Ismail Gögenur, Julie Gehl, Lene Baeksgaard, Rajendra Singh Garbyal, Michael Patrick Achiam

Journal: Journal of cancer research and clinical oncology 2023;149(17):16031-16042

PMID: 37688629

Abstract

PURPOSE

In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment.

METHODS

In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples.

RESULTS

Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased.

CONCLUSION

This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.

© 2023. The Author(s).

Address: Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [email protected].; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [email protected].; Center for Surgical Science, Department of Surgery, Zealand University Hospital, Koege, Denmark.; Graduate School of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Oncology and Palliative Care, Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Zealand University Hospital, Roskilde, Denmark.; Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
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