Circulating Levels of the Proinflammatory Monomeric Isoform of C-Reactive Protein (mCRP) Correlate with Intra-Tumoral mCRP Abundance in Stage II-III Colon Cancer Patients.

PURPOSE: Colorectal cancer (CRC) is the third most common type of cancer worldwide. The link between inflammation and CRC is well established. Elevated levels of C-reactive protein (CRP) upon diagnosis is a known negative prognostic factor for CRC patients. Monomeric CRP (mCRP) has been demonstrated in tissues of several diseases associated with inflammation, including colon cancer (CC). mCRP possesses proinflammatory properties and is a possible mediator of tumor-promoting inflammation. This study aimed to detect and quantify circulating mCRP and assess potential correlations with clinical CRP and intra-tumoral mCRP in CC patients. PATIENTS AND METHODS: Forty patients treated for stage II-III CC between 2012 and 2015 at Sorlandet Hospital, Norway, were included in the study. Twenty patients had CRP level <10 mg/l and 20 patients had CRP ≥10 mg/l, measured routinely at diagnosis (clinical CRP). EDTA plasma was used for mCRP detection by enzyme-linked immunosorbent assay (ELISA; n = 40) and mass spectrometry (MS; n = 20) (MS data are available via ProteomeXchange with identifier PXD046746). Tumor mCRP abundance was classified into three categories by reference scoring, using an antigen-retrieval technique on formalin-fixed paraffin-embedded tissue samples (n = 29). RESULTS: Circulating mCRP levels were detectable by both ELISA and MS. Median mCRP level measured by ELISA was 2.55 ng/mL, while the MS analysis detected 19.02 ng/mL. Both analyses exhibited significant correlations with clinical CRP (ELISA, p = 0.012; MS, p < 0.001). Intra-tumoral mCRP correlated with circulating mCRP measured by MS (p < 0.001) and with clinical CRP (p < 0.001). CONCLUSION: To the authors' knowledge, this is the first report of mCRP in the circulation of cancer patients. By employing two different analytical methods, mCRP was reliably detected in CC patients. Patients with elevated circulating mCRP measured by MS had higher intra-tumoral mCRP abundance. The interesting correlation of circulating and intra-tumoral mCRP levels may represent another facet of the interplay between local and systemic inflammation in CC patients.