36P Plasma levels of hsa_circ_0001445 and hsa_circ_0007915 may indicate the presence of metastatic disease in patients with colorectal cancer

Circular RNAs (circRNAs) are group of special endogenous long non-coding RNAs (ncRNAs). Their circular form makes them resistant to exonuclease activity compared to linear ncRNAs and thus more suitable as new biomarkers. The aim of our study was to evaluate the expressions of two circRNAs – hsa_circ_0001445 and hsa_circ_0007915 in patients with colorectal cancer (CRC) in different stages of disease in comparison with healthy volunteers (HV). 122 patients with metastatic CRC (mCRC), 29 adjuvant patients with stage III disease who had undergone radical surgery and postoperative chemotherapy and 90 HV were investigated. All adjuvant patients had normal levels of CEA and they were followed-up regularly for 1 year after the end of their treatment and had no signs of radiological or biochemical relapse. CicrRNAs were extracted from patients’ plasma obtained prior to chemotherapy using a commercial kit. The circRNAs expression levels in plasma samples were measured by qPCR and the relative expression was calculated applying 2-ΔΔCt method. Patients with mCRC had significantly higher expression of hsa_circ_0001445 and hsa_circ_0007915 than adjuvant patients and HV. At the optimal cut-off values for their plasma levels, hsa_circ_0001445 and hsa_circ_0007915 could significantly distinguish between patients with or without metastatic disease with 92.56% sensitivity and 42.86% specificity and with 86.07% sensitivity and 57.14% specificity (AUC=0.729, 95% CI: 0.62-0.84, p=0.0002; AUC=0.714, 95% CI: 0.59-0.84, p=0.0004), respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months (95% CI: 24.99-34.73) in comparison with the mean OS of the patients with low expression – 20 months (95% CI: 16.70-23.76) (log-rank test, p=0.034). In multivariate Cox regression analysis the low levels of hsa_circ_0001445 were also associated with shorter survival (HR=1.59, 95% CI: 1.02-2.47, p=0.040). Our results indicate that hsa_circ_0001445 in plasma has prognostic significance and the two circRNAs may be useful to differentiate metastatic from non-metastatic CRC patients.