Colorectal cancer (CRC) is the second leading cause of cancer death in New Zealand. Diagnostic delay and inaccurate risk assessments for treatment are two challenging areas that effect outcomes for CRC patients. Current screening and diagnostic approaches lack the ability to detect many early, more treatable CRC’s. Colonoscopies are invasive and costly while the fecal immunochemical screening test (FIT) lacks sensitivity. Furthermore, for patients diagnosed with mid-stage CRC it is currently not possible to accurately predict how patients will respond to treatment. This is particularly so for locally advanced rectal cancer (LARC) patients where only 15-27% of patients have a complete pathological response to long course chemoradiation (LCCR).
There is increasing interest in the field of small non-coding RNAs (sncRNAs) as circulating diagnostic and predictive biomarkers in CRC. Dysregulated sncRNAs are released from tumour cells within extracellular vesicles (EVs) and are therefore readily available in the blood. Thus sncRNA species in circulation are potentially markers of tumour burden and the host’s immune response.
The aim of this study is to utilise an unbiased approach to discover circulating sncRNA biomarker candidates for the early detection of CRC and predictors of response to LCCR.
Total RNA has been extracted from the plasma of healthy controls (n=20), stage I CRC patients (n=13), responders to LCCR (n=8) and non-responders to LCCR (n=12). Small RNA libraries have been constructed using the Bioo Scientific Nextflex V3 kit and are being sequenced on the NextSeq550. Differential expression analysis will be performed for controls vs stage I patients and responders vs non-responders to LCCR. Finally, extracellular packaging in EVs and tumour expression will be explored in differentially expressed sncRNA candidates.