The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer.
BACKGROUND
Elevated 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.


METHODS
CRP-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.


RESULTS
CRP-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.


CONCLUSIONS
CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhangxy@gzhmu.edu.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhangxy@gzhmu.edu.cn.|Department of Pathogenic Biology, Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510182, P.R. China. zhangxy@gzhmu.edu.cn.
Xue-Yan
XY
Zhang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, P.R. China. zhangge@mail.sysu.edu.cn.
Ge
G
Zhang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, P.R. China. jiangying304@hotmail.com.
Ying
Y
Jiang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. liudan@sysucc.org.cn.|Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. liudan@sysucc.org.cn.
Dan
D
Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. limzh@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. limzh@sysucc.org.cn.
Man-Zhi
MZ
Li
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhongqian@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhongqian@sysucc.org.cn.
Qian
Q
Zhong
Department of Gastrointestinal Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510180, P.R. China. shandabi@126.com.
Shan-Qi
SQ
Zeng
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. liuwl@sysucc.org.cn.|Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. liuwl@sysucc.org.cn.
Wan-Li
WL
Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zengmsh@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zengmsh@sysucc.org.cn.
Mu-Sheng
MS
Zeng
D015415:Biomarkers; D002097:C-Reactive Protein; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008175:Lung Neoplasms; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics; D012189:Retrospective Studies; D000685:Serum Amyloid A Protein
D015415:Biomarkers; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein