Identification, Validation, and Utilization of Immune Cells in Pancreatic Ductal Adenocarcinoma Based on Marker Genes

Willem de Koning; Diba Latifi; Yunlei Li; Casper H J van Eijck; Andrew P Stubbs; Dana A M Mustafa

doi:10.3389/fimmu.2021.649061

Identification, Validation, and Utilization of Immune Cells in Pancreatic Ductal Adenocarcinoma Based on Marker Genes

Front Immunol. 2021 Apr 27:12:649061. doi: 10.3389/fimmu.2021.649061. eCollection 2021.

Authors

Willem de Koning^{1

2}, Diba Latifi³, Yunlei Li^{1

2}, Casper H J van Eijck³, Andrew P Stubbs¹, Dana A M Mustafa²

Affiliations

¹ Unit of Clinical Bioinformatics, Department of Pathology, Erasmus University Medical Centre, Rotterdam, Netherlands.
² Tumor Immuno-Pathology Laboratory, Department of Pathology, Erasmus University Medical Centre, Rotterdam, Netherlands.
³ Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands.

Abstract

The immune response affects tumor biological behavior and progression. The specific immune characteristics of pancreatic ductal adenocarcinoma (PDAC) can determine the metastatic abilities of cancerous cells and the survival of patients. Therefore, it is important to characterize the specific immune landscape in PDAC tissue samples, and the effect of various types of therapy on that immune composition. Previously, a set of marker genes was identified to assess the immune cell composition in different types of cancer tissue samples. However, gene expression and subtypes of immune cells may vary across different types of cancers. The aim of this study was to provide a method to identify immune cells specifically in PDAC tissue samples. The method is based on defining a specific set of marker genes expressed by various immune cells in PDAC samples. A total of 90 marker genes were selected and tested for immune cell type-specific definition in PDAC; including 43 previously used, and 47 newly selected marker genes. The immune cell-type specificity was checked mathematically by calculating the "pairwise similarity" for all candidate genes using the PDAC RNA-sequenced dataset available at The Cancer Genome Atlas. A set of 55 marker genes that identify 22 different immune cell types for PDAC was created. To validate the method and the set of marker genes, an independent mRNA expression dataset of 24 samples of PDAC patients who received various types of (neo)adjuvant treatments was used. The results showed that by applying our method we were able to identify PDAC specific marker genes to characterize immune cell infiltration in tissue samples. The method we described enabled identifying different subtypes of immune cells that were affected by various types of therapy in PDAC patients. In addition, our method can be easily adapted and applied to identify the specific immune landscape in various types of tissue samples.

Keywords: immune cells; immune microenvironment; mRNA expression; marker genes; pancreatic ductal adenocarcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / immunology*
Biomarkers, Tumor / metabolism
Carcinoma, Pancreatic Ductal / genetics
Carcinoma, Pancreatic Ductal / immunology*
Carcinoma, Pancreatic Ductal / therapy
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic / genetics
Gene Expression Regulation, Neoplastic / immunology*
Humans
Immune System / cytology
Immune System / immunology*
Immune System / metabolism
Neoadjuvant Therapy / methods
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / immunology*
Pancreatic Neoplasms / therapy
Reproducibility of Results
Tumor Microenvironment / genetics
Tumor Microenvironment / immunology

Substances

Biomarkers, Tumor