Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in Aotearoa, with a mortality of over 1200 deaths annually and an incidence of over 6.57 per 1000 population per year. While being one of the most prevalent cancers worldwide, CRC incidence and mortality has been decreasing in recent decades, a trend that is associated with improved treatment methods and preventative screening programmes. However, while the incidence of CRC in individuals over the age of 50 has been decreasing, the incidence of EO-CRC has been increasing. The reasons for this are not yet fully understood. Growing evidence shows that early-onset colorectal cancer (EO-CRC), generally defined as CRC in individuals under the age of 50, may be distinct to later-onset colorectal cancer (LO-CRC).
The aim of this study was to investigate dysregulated ribonucleic acid (RNA) expression in EO-CRC by comparing the differences in RNA expression in patient tumours and adjacent mucosa. This study aimed to address gaps in the knowledge of EO-CRC by performing both whole transcriptome and small RNA sequencing and targeted microRNA (miRNA) RT-qPCR to give a comprehensive view of the entire transcriptomic landscape of EO-CRC in Aotearoa.
Pairs of tumour and adjacent mucosa tissue were collected from 13 EO-CRC patients at the time of surgery. RNA from each of the tumour and adjacent mucosa tissues was extracted and quality control was performed. This RNA was then sent to the Australian Genome Research Facility for whole transcriptome and small RNA sequencing. RT-qPCR was performed in a subset of the sequencing cohort to investigate the expression of miR-221-3p, miR-101-3p, miR-125a-5p, miR-181a-5p, miR-203a-3p, miR-223-3p, and 2 miR-185-5p. Tissue sectioning with H&E staining was used to visualise histological typing of tumours.
We found a statistically significant difference in the expression of miR-125-5p and miR-203a-3p between the tumour and adjacent mucosa groups (p=0.0083 and p=0.0343 respectively). While not statistically significant, we also found trends in the change in expression of miR-181a-5p an miR-223-3p.
While further research in bigger cohort sizes is required to confirm trends in RNA expression, our findings demonstrate differential RNA expression in an Aotearoa-specific EO-CRC cohort. Identifying the expression profile of EO-CRC is important for differentiating EO-CRC as a distinct disease from LO-CRC. It is also important for optimising RNA-based biomarkers and treatment for CRC in young people, and better understanding the contributing factors to EO-CRC could help develop methods for early detection and prevention.