Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties.
Maria TabusoRaghu AdyaRichard StarkKishore GopalakrishnanYee Wah TsangSean JamesAndrew WhiteAdrian FiskFederica DimitriMark ChristianRamesh Pulendran ArasaradnamPublished in: International journal of molecular sciences (2021)
The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (COL1A1) p = 0.007; secreted frizzled related protein (SFRP2) p = 0.057; fibroblast growth factor 7 (FGF7) not significant (ns); phospholipase A2, group IIA (PLA2G2A) ns; nerve growth factor receptor (NGFR) ns; lymphoid enhancer binding factor 1 (LEF1) p = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (CDH1) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. COL1A1 and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. COL1A1 may represent a stromal prognostic biomarker and therapeutic target in colon cancer.
Keyphrases
- adipose tissue
- cell cycle
- growth factor
- genome wide
- extracellular matrix
- insulin resistance
- high fat diet
- genome wide identification
- cell proliferation
- transcription factor
- endothelial cells
- bioinformatics analysis
- end stage renal disease
- stem cells
- papillary thyroid
- lymph node
- ejection fraction
- squamous cell
- dna methylation
- small cell lung cancer
- binding protein
- cell migration
- induced pluripotent stem cells
- genome wide analysis
- metabolic syndrome
- chronic kidney disease
- gene expression
- staphylococcus aureus
- systemic sclerosis
- minimally invasive
- single cell
- peritoneal dialysis
- escherichia coli
- biofilm formation
- childhood cancer
- zika virus
- tissue engineering
- patient reported outcomes
- prognostic factors
- young adults
- dna binding