DNA methylation of SOCS1/2/3 predicts hepatocellular carcinoma recurrence after liver transplantation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-02-01

AUTHORS

Zhentao Yang, Hai Zhu, Liang Zhang, Qiang Wei, Lin Zhou, Xiao Xu, Penghong Song, Jialin Liu, Haiyang Xie, Shusen Zheng

ABSTRACT

DNA methylation status of SOCS1/SOCS2/SOCS3 is intensely involved in the development and progression of hepatocellular carcinoma (HCC). This study explored its prognostic value for HCC recurrence after liver transplantation (LT). Clinical data from 62 HCC patients who underwent LT at our centre were retrospectively collected. The SOCS1/2/3 methylation level were determined using next generation sequencing. Overall, 244 methylated sites at the SOCS1/2/3 promoter were identified. Multivariate analysis yielded the methylated sites SOCS2-1-90 (Chromosome 12, Position 93963982; HR 0.386, 95% CI 0.149–0.998) and SOCS1-1-68 (Chromosome 16, Position 11350699; HR 4.376, 95% CI 1.324–14.459) as independent predictors of post-LT HCC recurrence. Patients were divided into highly- and lowly methylated groups according to the median SOCS1-1-68 (0.95%) and SOCS2-1-90 (1.05%) methylation levels. Highly methylated SOCS2-1-90 was associated with significantly lower AFP levels (P = 0.008), decreased proportion of maximal tumour size > 8 cm (P = 0.02), and better pathological grading (P = 0.06). Conversely, patients in the highly methylated SOCS1-1-68 group had higher AFP levels (P = 0.043). Kaplan–Meier analyses revealed that patients with highly methylated SOCS2-1-90 had increased recurrence free survival (RFS) and overall survival (OS) rates when compared with those with lowly methylated SOCS2-1-90 (P = 0.0041 and 0.012, respectively). Nevertheless, the correlation between methylated SOCS1-1-68 and cumulative recurrence rates was less pronounced (P = 0.098). Subgroup analyses demonstrated that patients meeting the Milan criteria, UCSF criteria, Metroticket 2.0 Model or Hangzhou criteria with highly methylated SOCS2-1-90 had the best RFS rates. DNA methylation of SOCS2-1-90 is a novel biomarker for predicting post-transplant HCC recurrence. More... »

PAGES

1773-1782

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11033-020-05271-3

DOI

http://dx.doi.org/10.1007/s11033-020-05271-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1124459594

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32006198


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33 schema:description DNA methylation status of SOCS1/SOCS2/SOCS3 is intensely involved in the development and progression of hepatocellular carcinoma (HCC). This study explored its prognostic value for HCC recurrence after liver transplantation (LT). Clinical data from 62 HCC patients who underwent LT at our centre were retrospectively collected. The SOCS1/2/3 methylation level were determined using next generation sequencing. Overall, 244 methylated sites at the SOCS1/2/3 promoter were identified. Multivariate analysis yielded the methylated sites SOCS2-1-90 (Chromosome 12, Position 93963982; HR 0.386, 95% CI 0.149–0.998) and SOCS1-1-68 (Chromosome 16, Position 11350699; HR 4.376, 95% CI 1.324–14.459) as independent predictors of post-LT HCC recurrence. Patients were divided into highly- and lowly methylated groups according to the median SOCS1-1-68 (0.95%) and SOCS2-1-90 (1.05%) methylation levels. Highly methylated SOCS2-1-90 was associated with significantly lower AFP levels (P = 0.008), decreased proportion of maximal tumour size > 8 cm (P = 0.02), and better pathological grading (P = 0.06). Conversely, patients in the highly methylated SOCS1-1-68 group had higher AFP levels (P = 0.043). Kaplan–Meier analyses revealed that patients with highly methylated SOCS2-1-90 had increased recurrence free survival (RFS) and overall survival (OS) rates when compared with those with lowly methylated SOCS2-1-90 (P = 0.0041 and 0.012, respectively). Nevertheless, the correlation between methylated SOCS1-1-68 and cumulative recurrence rates was less pronounced (P = 0.098). Subgroup analyses demonstrated that patients meeting the Milan criteria, UCSF criteria, Metroticket 2.0 Model or Hangzhou criteria with highly methylated SOCS2-1-90 had the best RFS rates. DNA methylation of SOCS2-1-90 is a novel biomarker for predicting post-transplant HCC recurrence.
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40 DNA methylation
41 DNA methylation status
42 HCC patients
43 HCC recurrence
44 Hangzhou criteria
45 Kaplan-Meier analysis
46 Metroticket 2.0 model
47 Milan criteria
48 RFS rates
49 SOCS3
50 UCSF criteria
51 analysis
52 better RFS rate
53 biomarkers
54 carcinoma
55 carcinoma recurrence
56 center
57 clinical data
58 correlation
59 criteria
60 cumulative recurrence rate
61 data
62 development
63 free survival
64 generation sequencing
65 grading
66 group
67 hepatocellular carcinoma
68 hepatocellular carcinoma recurrence
69 high AFP levels
70 independent predictors
71 levels
72 liver transplantation
73 low AFP levels
74 lowly
75 maximal tumor size
76 methylated sites
77 methylation
78 methylation levels
79 methylation status
80 model
81 multivariate analysis
82 next-generation sequencing
83 novel biomarkers
84 overall survival rate
85 pathological grading
86 patients
87 post-LT HCC recurrence
88 post-transplant HCC recurrence
89 predictors
90 prognostic value
91 progression
92 promoter
93 proportion
94 rate
95 recurrence
96 recurrence rate
97 recurrence-free survival
98 sequencing
99 sites
100 size
101 status
102 study
103 subgroup analysis
104 survival
105 survival rate
106 transplantation
107 tumor size
108 values
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