Colony-stimulating factor 3 signaling in colon and rectal cancers: Immune response and CMS classification in TCGA data

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.

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

“…CSF3R is a type 1 cytokine receptor, encoding the receptor for granulocyte colony-stimulating factor (G-CSF) and playing a crucial role in granulocyte proliferation and differentiation (64,65). The altered CSF3R expression or activating heterozygous variants in CSF3R have been identified as risk factors in the development of multiple malignancies, such as colorectal cancer, myeloid malignancies and lymphoid malignancies (65)(66)(67). This is particularly the case for mutations in CSF3R commonly present in chronic neutrophilic leukaemia or atypical chronic myeloid leukaemia (68).…”

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

“…Signaling pathway include immune system [69], neutrophil degranulation [70], cytokine signaling in immune system [71], extracellular matrix organization [72], post-translational protein phosphorylation [73], biological oxidations [74], metabolism [75] and metabolism of lipids [76] were responsible for progression of CD. CXCL5 [77], CXCL3 [78], PROK2 [79], CXCR1 [80], PYCR1 [81], OSM (oncostatin M) [82], IL15RA [83], LRG1 [84], LCN2 [85], BATF2 [86], CXCL1 [87], S100A9 [88], IFITM1 [89], MYOF (myoferlin) [90], XBP1 [91], MMP3 [92], TAP1 [93], FPR2 [94], CXCL6 [95], C2CD4A [96], IFITM3 [97], IL1B [98], SLC6A14 [99], FPR1 [100], NOS2 [101], CHI3L1 [102], TGM2 [103], MUC4 [104], TREM1 [105], WNT5A [106], HGF (hepatocyte growth factor) [107], CXCL9 [108], GBP1 [109], S100A11 [110], ADM (adrenomedullin) [111], CXCL11 [112], CXCL10 [113], LILRB2 [114], GDF15 [115], IL1RN [116] STAT1 [117], SLAMF7 [105], CYP27B1 [118], NETO2 [119], TFPI2 [120], ZC3H12A [121], MMP1 [122], CSF3 [123], SOCS3 [124], TLR8 [125], HTRA3 [126], CEBPB (CCAAT enhancer binding protein beta) [127], CD55 [128], CXCR2 [129], CCL28 [130], CBR3 [131], CCL3 [132], FCGR2A [48], ACSL1 [133], CCL2 [134], SOD2 [135], CD14 [136], IGFBP2 [137], CD274 [138], DERL3 [139], SERPINE1 [140], IDO1 [141], PDK...…”

Tocotrienol-rich Fraction Modulated Genes Responsible for Inflammation in Lipopolysaccharide-stimulated RAW 264.7 Macrophages

“…The macrophage inflammatory protein-2 (MIP-2), also known as the CXCL2, is a critical chemokine for neutrophils that is produced in the rat intestine in response to platelet-activating factor (PAF) and to mediate intestinal inflammation and injury [29].CSF3 is a co-stimulator of inflammation and autoimmunity and is associated with changes to the immune environment in colorectal cancer animal models [30]. This study showed that CXCL2 and CSF3genes were downregulated in the TRF-treated group compared to the LPS-only group.…”

“…This study showed that CXCL2 and CSF3genes were downregulated in the TRF-treated group compared to the LPS-only group. Inhibition of these genes reduced inflammation in several diseases [30].…”