title: High-sensitivity C-reactive protein complements plasma Epstein-Barr virus deoxyribonucleic acid prognostication in nasopharyngeal carcinoma: a large-scale retrospective and prospective cohort study.
abstract: OBJECTIVE
  To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
  
  
  RESULTS
  Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
  
  
  CONCLUSIONS
  Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Lin-Quan
authors.initials: LQ
authors.lastname: Tang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Information Technology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Chao-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yun-Xiu-Xiu
authors.initials: YX
authors.lastname: Xu
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Dong-Peng
authors.initials: DP
authors.lastname: Hu
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Wen
authors.affiliation: ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yu-Tuan
authors.initials: YT
authors.lastname: Peng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Huai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Clinical Laboratory, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ka-Jia
authors.initials: KJ
authors.lastname: Cao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address: zengmsh@sysucc.org.cn.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis*; D002277:Carcinoma; D002681:China / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D002097:C-Reactive Protein