Using bioinformatics approaches to investigate driver genes and identify BCL7A as a prognostic gene in colorectal cancer

Colorectal cancer (CRC) results from the uncontrolled growth of cells in the colon, rectum, or appendix. The 5-year relative survival rate for patients with CRC is 65% and is correlated with the stage at diagnosis (being 91% for stage I at diagnosis versus 12% for stage IV). This study aimed to identify CRC driver genes and prognostic genes for aiding cancer panel design to detect gene mutations in clinical early-stage screening. First, we utilized bioinformatics approaches to analyze 354 paired sequencing profiles from The Cancer Genome Atlas (TCGA) to find CRC driver genes and to analyze the sequencing profiles of 38 patients with >5 years of follow-up data to search for prognostic genes. The results revealed eight driver genes and ten prognostic genes. Next, the detection of these mutated genes was verified using tissues and blood from Taiwanese CRC patients. The results showed that the set of mutated genes provides high coverage in driver gene screening, and that APC, TP53, PIK3CA, and FAT4 could be detected in blood as ctDNA test targets. We further found that BCL7A gene mutation was correlated with prognosis in CRC (log-rank p-value=0.02), and that mutations of BCL7A could be identified in ctDNA samples. These findings may be of value in clinical early cancer detection, disease monitoring, drug development, and treatment efforts in the future.