The effect of gene alterations on the overall survival in colon cancer patients: An in-depth statistical analysis of the cBioPortal database

Abstract

Colorectal cancer (CRC) is the 3rd most common cancer worldwide and the 4th most registered cancer in the UK. Of CRC patients, 66.7% have colon cancer (CCA). Factors affecting CCA development are mostly lifestyle and environmental factors. In CCA, transforming the colonic's epithelium into a precancerous lesion and later to invasive cancer is caused by an accumulation of gene mutations. The gold standard treatment for CCA is surgical resection. Genes’ targeted therapies showed a significant improvement of the overall survival (OS). This project aims to produce a predictive model for patient outcomes, the biochemical effect of the selected genes and their mutations and create a personalised medicine scheme for CCA patients. This project utilizes the cBioPortal database to find the most common mutated genes in CCA patients with mutations of 5% or more, and correlate those mutations with OS. The significance of the difference between the gene types (wild-type and altered) was determined using the Wilcoxon test. The significance of the patients’ characteristics was determined using crosstabulations and the chi-square test. Kaplan-Meyer analysis of these genes used to predict the expected OS for CCA patients. The study was performed on 1272 CCA patients. It showed that alterations to adenomatous polyposis coli (APC), tumour protein 53 (TP53), protein tyrosine phosphatase receptor type T (PTPRT), and SRC proto-oncogene, non-receptor tyrosine kinase (SRC) were associated with improved survival. Conversely, alterations to B-Raf proto-oncogene, serine/threonine kinase (BRAF), RNA binding protein, fox-1 homolog (RBFOX1), F-Box and WD repeat domain containing 7 (FBXW7), CUB And Sushi multiple domains 1 (CSMD1), WW domain-containing oxidoreductase (WWOX), and mono-ADP ribosylhydrolase 2 (MACROD2) were associated with worse survival. Furthermore, alterations to titin (TTN) and spectrin repeat-containing nuclear envelope protein 1 (SYNE1) were associated with 0% 5-year survival. More studies should be done to determine the effect of more CCA patients’ characteristics and their OS. Additionally, more gene-specific targeted therapies should be developed to improve CCA patients’ OS.