P-232 Prognostic inflammatory and microRNA biomarkers in stage IV colorectal cancer patients

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC patients have poor prognosis with a five-year survival rate of 14%. Systemic inflammation has a key determinant role in clinicopathological outcomes among CRC patients. Furthermore, microRNA (miRNA), small RNA non-coding molecules, have been detected to be dysregulated in tissues, as well as in biological fluids taken from colorectal cancer patients. Consequently, we are interested in investigating the prognostic potential of inflammatory markers and miRNA in Stage IV colorectal cancer patients. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum albumin, fibrinogen, ferritin, haptoglobin, lymphocyte/monocyte ratio, neutrophil/lymphocyte ratio and platelets/lymphocytes ratio, and Glasgow prognostic score were prospectively evaluated pre-chemotherapy in 67 Stage IV CRC patients presenting at the American University of Beirut Medical Center between May 2018 till November 2020. miRNA (miR-21, miR-19a, miR-23a, miR-29a, miR-155, miR-210, miR-145, miR-203, miR-31 and miR-345) expression was determined using reverse transcription real-time PCR in plasma samples collected prechemotherapy. Cutoff values of the biomarkers were determined using ROC curve. Statistical analysis was performed with SPSS version 25. The median overall survival for the 67 patients was not reached and the median progression-free survival was 13 months. Patients with low pre-chemotherapy WBC count (< 9600 /cu.mm), CRP (< 3.1 mg/L) or ESR (< 20.5 mm/hr) experienced significant improvements in progression-free survival (P=0.012, P=0.016, P < 0.05 respectively) compared with patients with high pre-chemotherapy CRP, ESR or WBC count. Patients with low pre-chemotherapy haptoglobin (< 3.1 g/L) had significantly better overall survival (OS) (P < 0.05) compared with patients with high pre-chemotherapy haptoglobin. Low levels of miR-23a and miR-19a were significantly associated with better PFS (P=0.021 and P=0.031 respectively). Elevated levels of miR-345 and miR-210 were correlated with better OS (P=0.029 and P=0.035 respectively). Subsequent Cox regression multivariate analysis showed that high pre-chemotherapy of CRP, WBC count, miR-19a, and miR-23a were independent favorable prognostic factors for PFS with a HR=3.8; 95%CI: 1.149-12.648; HR=2.426; 95%CI: 1.159-5.075, HR= 2.37; 95%CI: 1.092-5.15 and, HR=2.31; 95%CI: 1.029-4.414), respectively. CRP level, WBC count, miR-19a, and miR-23a are potential prognostic biomarkers for progression-free survival in Stage IV colorectal cancer that need further validation in larger cohorts.