CRP activates the complement pathway. It is a pattern recognition receptor with a pentameric polypeptide structure, which binds to a variety of intrinsic and extrinsic ligands. CRP’s highest affinity is towards phosphocholine residues. CRP is produced only in hepatocytes under the transcriptional control of interleukin-6 (IL-6).1 Circulating levels of CRP increase hundred-fold in response to infections and inflammation. Determination of CRP levels is one of the most solicited laboratory tests. The literature documents an increase
in CRP levels in cancer patients. High CRP levels AZD0530 nmr may be of prognostic value since they are associated with poor survival. Among gastrointestinal tumors, esophageal,2 gastric,3 colorectal,4 and pancreatic cancers5 have reported this association. Mechanistically, high CRP levels are either a marker of reactive inflammation to a tumor or a marker of an ongoing inflammatory process that favored tumor development.
Tumors frequently show histological evidence of intratumoral and/or peritumoral inflammation. Necrotic cells release proinflammatory signals, which attract inflammatory cells from the surrounding tissue. This inflammatory response may foster the tumoral process rather than contain it. Inflammatory cells help to stimulate and to sustain angiogenesis and promote invasiveness by degrading the extracellular matrix. Inflammation is learn more now recognized as an enabling characteristic of tumors.6 CRP has gained prognostic value in hepatocellular carcinoma (HCC). In a cohort of 90 HCC patients, Nagaoka et al.7 found that CRP levels above 3 mg/dL were predictive of poor prognosis and a decreased survival rate. In patients undergoing resection for HCC, Methisazone preoperative CRP levels correlated with tumor size and vascular invasion and were predictive of early recurrence.8 In the transplantation
setting, high preoperative CRP levels were related to tumor recurrence and poor overall survival; in those specific patients with HCC beyond Milan criteria, high CRP levels were an independent predictor of poor outcome.9 Finally, in a prospective evaluation of a cohort of 133 patients with newly diagnosed HCC, Kinoshita et al.10 reported that CRP levels above 1 mg/dL predicted a shorter survival and were characteristic of high Child-Pugh, CLIP, and JIS scores. In this issue of Hepatology, Peck-Radosavljevic and co-workers11 investigated the value of serum CRP levels in a large cohort of 615 HCC patients who were not amenable to surgery. The hazard ratio of death increased with CRP values up to 2.5 mg/dL, but not beyond. CRP levels above 1 mg/dL were significantly and independently associated with poor survival upon multivariate analysis in the discovery and in the validation cohorts. Patients with a CRP above 1 mg/dL at diagnosis had a survival of 4 months compared to 20 months for patients with a CRP below 1 mg/dL.