Fluoropyrimdine therapy induced alterations in interleukins expression in colorectal cancer patients

Abstract

This study monitored the changes in the expression of inflammatory IL-6 and IL-1β during the treatment period of Fluoropyrimidine (FP) based therapy. RNA was extracted from the peripheral blood of 102 CRC patients before treatment with FP therapy, and from 48 and 32 patients after 3 and 6 months of treatment, respectively. The genetic transcription of IL-6 and IL-1β was determined by real time PCR. Patients were stratified according to their levels of IL-6 and IL-1β genes expression for subgroup and survival analyses. Baseline CRC patients showed overexpression of IL-6 and IL-1β compared to healthy control. FP therapy significantly induced IL-6 and IL-1β expression. Subgroup analysis showed that patients with right colon tumors had significant elevation in both IL-6 and IL-1β with FP therapy. FP therapy significantly induced IL-1β expression in patients ⩽45 years, smokers, with high baseline level of CA19.9, right colon tumors, low grade pathology, T3 tumors and positive lymph nodes. Survival analysis showed that baseline levels of interleukins expression had insignificant effect on overall survival and event free survival. FP therapy has an impact on the level of interleukins expression declared in certain clinicopathological subgroups of CRC patients, but without a prognostic significance on patients' survival.

Keywords: colorectal cancer; fluoropyrimidine therapy; interleukins expression.

Figure 1.

(a) IL-6 expression in healthy control and baseline CRC patients. (b) The change in IL-6 expression after 3 and 6 months of FP therapy normalized to their baseline levels in CRC patients.

Figure 2.

(a) IL-1β expression in healthy control and baseline CRC patients. (b) The change in IL-1β expression after 3 and 6 months of FP therapy normalized to their baseline levels in CRC patients. ^aSignificant difference when CRC patients after 3 and 6 months of FP therapy were compared with their baseline level, P value ⩽0.05. ^bSignificant difference when CRC patients after 6 months of FP therapy were compared with their level after 3 months of FP therapy, P value ⩽0.05.

Figure 3.

Kaplan-Meier analysis of OS for IL-6 (a) and IL-1β (b), EFS for IL-6 (c), and IL-1β (d). Baseline CRC patients were stratified into two groups of over-expression and under-expression around their median expression level of IL-6 and IL-1β normalised to β-actin.