PMID- 28068175
OWN - NLM
STAT- MEDLINE
DCOM- 20170802
LR  - 20220311
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 35
IP  - 7
DP  - 2017 Mar
TI  - CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular 
      Carcinoma: Results From a Multicenter Study.
PG  - 734-742
LID - 10.1200/JCO.2016.68.2153 [doi]
AB  - Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed 
      increasingly, and in one half of diagnosed patients, recurrence will develop. 
      Thus, it is urgent to identify recurrence-related markers. We investigated the 
      effectiveness of CpG methylation in predicting recurrence for patients with 
      E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four 
      independent centers were sorted by three phases. In the discovery phase, 66 tumor 
      samples were analyzed using the Illumina Methylation 450k Beadchip. Two 
      algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector 
      Machine-Recursive Feature Elimination, were used to select significant CpGs. In 
      the training phase, penalized Cox regression was used to further narrow CpGs into 
      140 samples. In the validation phase, candidate CpGs were validated using an 
      internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results 
      After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector 
      Operation and the Support Vector Machine-Recursive Feature Elimination 
      algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 
      3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase 
      inhibitor 3 were highlighted as candidate predictors in the training phase. On 
      the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was 
      developed to classify patients into high- and low-risk recurrence groups in the 
      training cohort ( P < .001). The performance of MSEH was validated in the 
      internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = 
      .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, 
      hepatitis B virus surface antigen, and antivirus therapy was generated to predict 
      the 5-year recurrence-free survival in the training cohort, and it performed well 
      in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, 
      respectively). Conclusion MSEH, a three-CpG-based signature, is useful in 
      predicting recurrence for patients with E-HCC.
FAU - Qiu, Jiliang
AU  - Qiu J
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Peng, Baogang
AU  - Peng B
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Tang, Yunqiang
AU  - Tang Y
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Qian, Yeben
AU  - Qian Y
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Guo, Pi
AU  - Guo P
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Li, Mengfeng
AU  - Li M
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Luo, Junhang
AU  - Luo J
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Chen, Bin
AU  - Chen B
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Tang, Hui
AU  - Tang H
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Lu, Canliang
AU  - Lu C
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Cai, Muyan
AU  - Cai M
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Ke, Zunfu
AU  - Ke Z
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - He, Wei
AU  - He W
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Zheng, Yun
AU  - Zheng Y
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Xie, Dan
AU  - Xie D
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Li, Binkui
AU  - Li B
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Yuan, Yunfei
AU  - Yuan Y
AD  - Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, Dan Xie, Binkui Li, and Yunfei Yuan, 
      Sun Yat-sen University Cancer Center; Baogang Peng, Junhang Luo, Bin Chen, and 
      Zunfu Ke, First Affiliated Hospital of Sun Yat-sen University; Pi Guo and 
      Mengfeng Li, Sun Yat-sen University; Jiliang Qiu, Muyan Cai, Wei He, Yun Zheng, 
      Dan Xie, Binkui Li, and Yunfei Yuan, State Key Laboratory of Oncology in South 
      China and Collaborative Innovation Center for Cancer Medicine; Jiliang Qiu, 
      Yunqiang Tang, and Hui Tang, Guangzhou Medical University Cancer Center, 
      Guangzhou; and Yeben Qian and Canliang Lu, First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170109
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
SB  - IM
CIN - J Clin Oncol. 2017 Mar;35(7):793-795. PMID: 28113009
CIN - J Clin Oncol. 2017 Jun 20;35(18):2097-2098. PMID: 28398848
CIN - J Clin Oncol. 2017 Jun 20;35(18):2098-2099. PMID: 28398849
MH  - Algorithms
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - Cohort Studies
MH  - *CpG Islands
MH  - *DNA Methylation
MH  - Female
MH  - Humans
MH  - Liver Neoplasms/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - *Models, Genetic
MH  - Neoplasm Recurrence, Local/*genetics/pathology
MH  - Neoplasm Staging
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Proportional Hazards Models
MH  - Reproducibility of Results
MH  - Support Vector Machine
MH  - Transcriptome
EDAT- 2017/01/10 06:00
MHDA- 2017/08/03 06:00
CRDT- 2017/01/10 06:00
PHST- 2017/01/10 06:00 [pubmed]
PHST- 2017/08/03 06:00 [medline]
PHST- 2017/01/10 06:00 [entrez]
AID - 10.1200/JCO.2016.68.2153 [pii]
AID - 10.1200/JCO.2016.68.2153 [doi]
PST - ppublish
SO  - J Clin Oncol. 2017 Mar;35(7):734-742. doi: 10.1200/JCO.2016.68.2153. Epub 2017 
      Jan 9.