Differential gene expression of tumor-infiltrating CD33 + myeloid cells in advanced- versus early-stage colorectal cance
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ORIGINAL ARTICLE
Differential gene expression of tumor‑infiltrating CD33+ myeloid cells in advanced‑ versus early‑stage colorectal cancer Salman M. Toor1 · Rowaida Z. Taha1 · Varun Sasidharan Nair1 · Reem Saleh1 · Khaled Murshed2 · Mohamed Abu Nada3 · Eyad Elkord1 Received: 14 July 2020 / Accepted: 13 September 2020 © The Author(s) 2020
Abstract Colorectal cancer (CRC) has high mortality rates, especially in patients with advanced disease stages, who often do not respond to therapy. The cellular components of the tumor microenvironment are essentially responsible for dictating disease progression and response to therapy. Expansion of different myeloid cell subsets in CRC tumors has been reported previously. However, tumor-infiltrating myeloid cells have both pro- and anti-tumor roles in disease progression. In this study, we performed transcriptomic profiling of cells of myeloid lineage (CD33+) from bulk CRC tumors at varying disease stages. We identified differentially expressed genes and pathways between CRC patients with advanced stage and early stages. We found that pro-angiogenic and hypoxia-related genes were upregulated, while genes related to immune and inflammatory responses were downregulated in C D33+ myeloid cells from patients with advanced stages, implying that immune cell recruitment and activation could be compromised in advanced disease stages. Moreover, we identified a unique “poor prognosis C D33+ gene signature” by aligning top upregulated and downregulated genes in tumor-infiltrating myeloid cells from our analyses with data from The Cancer Genome Atlas. Our results showed that this gene signature is an independent prognostic indicator for disease-specific survival in CRC patients, potentially reflecting its clinical importance. Keywords Colorectal cancer · Tumor microenvironment · Myeloid cells · Transcriptomics Abbreviations CRC Colorectal cancer DAVID Database for annotation, visualization and integrated discovery DSS Disease-specific survival DEGs Differentially expressed genes ICI Immune checkpoint inhibitor MDSC Myeloid-derived suppressor cell PCA Principle component analysis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02727-0) contains supplementary material, which is available to authorized users. * Eyad Elkord [email protected]; [email protected] 1
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box: 34110, Doha, Qatar
2
Department of Pathology, Hamad Medical Corporation, Doha, Qatar
3
Department of Surgery, Hamad Medical Corporation, Doha, Qatar
PFI Progression-free interval ppCD33sig Poor prognosis CD33 gene signature PPI Protein–protein interaction TAM Tumor-associated macrophage TAN Tumor-associated neutrophil TCGA The cancer genome atlas Treg T regulatory cell
Introduction Colorectal cancer (CRC) is the third leading cause of all cancer-related deaths in the world, and its incidence is
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