Molecular Biomarkers of Colorectal Cancer

Colorectal cancer (CRC) remains the third most common cause of cancer-related deaths in the UK. An insurmountable amount of pressure is present on endoscopy services from USC referrals, leaving a need for an accurate non-invasive method to screen and detect asymptomatic early CRC. The purpose of the study was to devise and validate a novel methodology for predicting disease-related dysregulated genes, that would have the potential to be used for screening, detection, or targeted therapies of CRC in the future. Identification of potential biomarkers related to CRC was performed by analysing different mechanisms that control gene expression; transcription factors (TFs), biological pathways (BPs), and gene co-expression. Information regarding these was available through various online databases. Twenty initial genes linked to CRC were identified. Analysis of TFs and BPs led to the prediction of 138 genes with potential to be used as biomarkers in CRC. The use of gene co-expression reduced the initial focus to 44 biomarkers; of which 42 were present in a commercially available CRC cell line. Using Quantitative PCR, these biomarkers were tested on 50 patient samples taken during the time of surgical resection. Individual gene expression ratios were then calculated and statistical analysis was performed using IBM SPSS® version 25. Sixteen of these genes showed statistically significant gene expression ratios (≥2) across the 50 patient samples. Cluster analysis followed by principal component analysis revealed the six most prevalent genes from the 16: BID, CCND1, CREB1, CTNNB1, IRS2 and MMP2. These key six genes are significantly dysregulated across 50 patient samples of CRC thus giving them a strong potential to be used for the purposes of screening, detection or targeted therapies in the future after much further interrogation.