Circulating levels of the pro-inflammatory monomeric isoform of C-reactive protein (mCRP) correlate with inflammatory markers in patients with stage II-III colon cancer.

Abstract

e15641 Background: Tumor-promoting inflammation is an established hallmark of cancer. C-reactive protein (CRP) is one of the most studied negative prognostic markers of the systemic inflammatory response (SIR) and known to be implicated in detrimental immune responses. Circulating CRP, as measured in routine practice, is a pentameric structure (pCRP). However, when pCRP binds to activated membranes, the protein dissociates into subunits termed monomeric CRP (mCRP). Pro-inflammatory characteristics of mCRP have been reported to be stronger than for pCRP. While a role for mCRP in cancer has been proposed, the circulating level of mCRP has never been investigated in cancer patients. Our aim was to detect and quantify plasma mCRP of patients diagnosed with stage II-III colon cancer (CC) and investigate possible correlations with other inflammatory markers. Methods: 40 patients treated for stage II-III CC between 2012 and 2015 at Sorlandet Hospital, Norway, were included in the study. 20 patients had pCRP level < 10 mg/L and 20 patients had pCRP > 10 mg/L, the latter interpreted as presence of SIR. Levels of pCRP and albumin were captured at the time of diagnosis. Pre-operative mCRP and the cytokines IL-6, IL-8 and TNFa were all measured using EDTA plasma samples. Pre-operative mCRP levels were measured by a specific ELISA employing reagents kindly provided by Drs. L. Potempa and I. Rajab (Roosevelt University, Schaumburg, IL). Results: Of the 40 patients, 47.5% were female, 57.5% had right-sided primary tumor and 50.0% were stage III. Median values (min-max) were for mCRP 2.55 ng/mL (0.00-10.9), pCRP 9.95 mg/L (0.50-136), IL-6 5.10 pg/mL (2.60-25.1), IL-8 4.95 pg/mL (0.40-32.4), TNFa 5.90 pg/mL (3.10-29.5) and albumin 40 g/L (29.0-46.0). Conclusions: To the authors’ knowledge, this is the first time mCRP has been reported in systemic circulation of cancer patients. Our study shows plasma mCRP to be quantifiable in CC patients, albeit at very low levels. This may be due to its reduced aqueous solubility and supports the notion of mCRP as a circulating particle-bound or tissue-associated isoform. However, despite low circulating mCRP levels and a small number of patients, mCRP still correlated with other well-known SIR markers with proven negative prognostic value in cancer patients, supporting its potential role as a pro-inflammatory player in CC. Further studies correlating SIR with circulating and tissue-bound mCRP are currently being performed. [Table: see text]