Abstract
Colorectal cancer is the 2nd leading cause of cancer-related deaths in the world. The mechanisms underlying CRC development, progression, and resistance to treatment are complex and not fully understood. The immune response in the tumor microenvironment has been shown to play a significant role in many cancers, including colorectal cancer. Colony-stimulating factor 3 (CSF3) has been associated with changes to the immune environment in colorectal cancer animal models. We hypothesized that CSF3 signaling would correlate with pro-tumor tumor microenvironment changes associated with immune infiltrate and response. We utilized publicly available datasets to guide future mechanistic studies of the role CSF3 and its receptor (CSF3R) play in colorectal cancer development and progression. Here, we use bioinformatics data and mRNA from patients with colon (n = 242) or rectal (n = 92) cancers, obtained from The Cancer Genome Atlas Firehose Legacy dataset. We examined correlations of CSF3 and CSF3R expression with patient demographics, tumor stage and consensus molecular subtype classification. Gene expression correlations, cell type enrichment, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data scores and Gene Ontology were used to analyze expression of receptor and ligand, tumor microenvironment infiltration of immune cells, and alterations in biological pathways. We found that CSF3 and CSF3R expression is highest in consensus molecular subtype 1 and consensus molecular subtype 4. Ligand and receptor expression are also correlated with changes in T cell and macrophage signatures. CSF3R significantly correlates with a large number of genes that are associated with poor colorectal cancer prognosis.
Highlights
Colorectal cancer (CRC) is the second most common cause of cancer-related deaths and the third most commonly diagnosed cancer world-wide [1]
We hypothesized that Colonystimulating factor 3 (CSF3) and CSF3 and its receptor (CSF3R) would correlate with male sex and increasing age
CSF3 and CSF3R correlate with specific consensus molecular subtypes (CMS) subtypes (CMS1 and CMS4) and immune gene signatures that have survival implications in CRC
Summary
The Cancer Genome Atlas (TCGA) colon and rectal cancer dataset. Available datasets of CC and RC (n = 92) patients were obtained from TCGA using either cBioPortal for Cancer Genomics or Xena browser (https://xenabrowser.net) [15, 16]. These datasets included de-identified patient demographics and RNA Seq data. Demographic data from CC (n = 242) and RC (n = 92) patients were obtained from TCGA using cBioPortal for Cancer Genomics [15, 17]. Potential demographic associations were assessed using high and low CSF3 and CSF3R expression levels stratified by the mean (TCGA Firehose Legacy RNA Seq V2 RSEM). A p-value of
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