Abstract
BackgroundElevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.MethodsCRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.ResultsCRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 ± 0.58 vs. 0.03 ± 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641–2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810–4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I–II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.ConclusionCRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.
Highlights
Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients
CRP is secreted by hepatocytes in response to the inflammatory cytokines produced by the tumor microenvironment [15], and CRP can enter the tumor microenvironment through the circulation, where it binds to a variety of autologous and extrinsic ligands and plays a key role in the clearance of tumor cells [16]
Identification of CRP‐serum amyloid A (SAA) complexes in the serum of lung cancer patients CRP-bound components in serum samples obtained from healthy controls or lung cancer patients were purified using anti-CRP carboxyl-coated polyethylene beads and subjected to SDS-PAGE
Summary
Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. Zhang et al Chin J Cancer (2015) 34:39 suggested that the elevation of serum C-reactive protein (CRP) could be used as a prognostic factor for lung cancer [10,11,12]. Autologous ligands include damaged cell membranes, apoptotic cells, plasma lipoproteins, phospholipids, ribonucleoprotein particles, extracellular matrix proteins, and Fc-γ receptors. CRP is secreted by hepatocytes in response to the inflammatory cytokines produced by the tumor microenvironment [15], and CRP can enter the tumor microenvironment through the circulation, where it binds to a variety of autologous and extrinsic ligands and plays a key role in the clearance of tumor cells [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
