PMID- 24495874
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20240323
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 110
IP  - 3
DP  - 2014 Feb 4
TI  - Using multiple cytokines to predict hepatocellular carcinoma recurrence in two 
      patient cohorts.
PG  - 733-40
LID - 10.1038/bjc.2013.781 [doi]
AB  - BACKGROUND: Cytokines are tightly linked to the carcinogenesis, development and 
      prognosis of hepatocellular carcinoma (HCC). We determined the prognostic value 
      of 39 circulating cytokines in HCC patients after radical resection and then 
      developed a novel cytokine-based prognostic classifier (CBPC) for the prediction 
      of patient prognosis. METHODS: A total of 179 patients were divided into two 
      cohorts based on the date of radical resection. Thirty-nine cytokines were 
      simultaneously analysed in patient serum samples using multiplex bead-based 
      Luminex technology. Support vector machine-based methods and Cox proportional 
      hazard models were used to develop a CBPC from the training cohort, which was 
      then validated in the validation cohort. RESULTS: Among seven cytokines 
      significantly correlating with the disease-free survival (DFS) in the training 
      cohort, six of them were validated to be significant prognostic factors to 
      predict DFS and overall survival (OS) in the validation cohort, namely fibroblast 
      growth factor 2 (FGF-2), growth-regulated oncogene (GRO), interleukin 8 (IL-8), 
      interferon gamma-induced protein 10 (IP-10), vascular endothelial growth factor 
      (VEGF), and interferon alpha-2 (IFN-alpha2). By integrating six cytokines and three 
      clinical characteristics, we developed a CBPC to predict the recurrence and 
      3-year OS of HCC patients (sensitivity, 0.648; specificity, 0.918). In the 
      validation cohort, the CBPC were confirmed to have significant predictive power 
      for predicting tumour recurrence and OS (sensitivity, 0.585; specificity, 0.857). 
      Interestingly, IFN-alpha2 was the only cytokine being independent prognostic factor 
      in both patient cohorts. CONCLUSION: Our study verifies the presence of specific 
      cytokine-phenotype associations with patient prognosis in HCC. The CBPC developed 
      include multiple circulating cytokines and may serve as a novel screening 
      approach for identifying HCC patients with a high risk of post-resection 
      recurrence and shorter OS. These individuals may also be suitable for 
      cytokine-targeted therapies.
FAU - Chen, Z-Y
AU  - Chen ZY
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China [3] 
      Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital of Sun 
      Yat-sen University, Guangzhou 510655, China.
FAU - Wei, W
AU  - Wei W
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China.
FAU - Guo, Z-X
AU  - Guo ZX
AD  - 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in 
      South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng 
      East Road, Guangzhou 510060, China [2] Department of Ultrasound, Sun Yat-Sen 
      University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
FAU - Peng, L-X
AU  - Peng LX
AD  - Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South 
      China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East 
      Road, Guangzhou 510060, China.
FAU - Shi, M
AU  - Shi M
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China.
FAU - Li, S-H
AU  - Li SH
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China.
FAU - Xiao, C-Z
AU  - Xiao CZ
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China [3] 
      Department of General surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou 
      Medical University, Shengzheng 518104, Guangdong, China.
FAU - Zhong, C
AU  - Zhong C
AD  - Department of Hepatobiliary Surgery, 1st Affiliated Hospital to Guangzhou 
      University of Chinese Medicine, 16 Jichang Road, Guangzhou 510405, China.
FAU - Qian, C-N
AU  - Qian CN
AD  - Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South 
      China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East 
      Road, Guangzhou 510060, China.
FAU - Guo, R-P
AU  - Guo RP
AD  - 1] Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 
      Dongfeng Road East, Guangzhou 510060, China [2] Sun Yat-sen University Cancer 
      Center, State Key Laboratory of Oncology in South China, Collaborative Innovation 
      Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131217
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Cytokines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Hepatocellular/*diagnosis/pathology
MH  - Cohort Studies
MH  - Cytokines/*biosynthesis
MH  - Disease-Free Survival
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Liver Neoplasms/*diagnosis/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*diagnosis/genetics
MH  - Prognosis
MH  - Proportional Hazards Models
PMC - PMC3915136
EDAT- 2014/02/06 06:00
MHDA- 2014/04/08 06:00
PMCR- 2015/02/04
CRDT- 2014/02/06 06:00
PHST- 2013/10/27 00:00 [revised]
PHST- 2013/11/17 00:00 [accepted]
PHST- 2014/02/06 06:00 [entrez]
PHST- 2014/02/06 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
PHST- 2015/02/04 00:00 [pmc-release]
AID - bjc2013781 [pii]
AID - 10.1038/bjc.2013.781 [doi]
PST - ppublish
SO  - Br J Cancer. 2014 Feb 4;110(3):733-40. doi: 10.1038/bjc.2013.781. Epub 2013 Dec 
      17.