title: Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma.
abstract: The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC.Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127-2.591) and PFS (HR, 1.767; 95 % CI, 1.168-2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC.
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.|Department of Gastroenterology, The Third Hospital of Nanchang City, Jiangxi 330009, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Yuening
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.|Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
authors.forename: Chengdong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Genetic and Metabolic Central Laboratory, The Maternal and Children Health Hospital of Guangxi, Guangxi 530002, China.
authors.forename: Qinle
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jiatong
authors.initials: J
authors.lastname: Li
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Feifan
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, China.
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Ruoheng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Dou
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China.
authors.forename: Jiezhen
authors.initials: J
authors.lastname: Liang
authors.affiliation: School of Public Health, Guangxi Medical University, Guangxi 530021, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Zhidi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Key Laboratory of Early Prevention and Treatment for Regional High Frequency, Ministry of Education, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Vanaparthy Pranay
authors.initials: VP
authors.lastname: Gupta
authors.affiliation: School of Public Health, Guangxi Medical University, Guangxi 530021, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D040501:Calgranulin A / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D040501:Calgranulin A
keywords: DNA methylation; S100A8; hepatocellular carcinoma; prognosis; pyrosequencing