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Title: Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer
Authors: Ling Z.-Q.
Lv P.
Lu X.-X.
Yu J.-L.
Han J.
Ying L.-S.
Zhu X.
Zhu W.-Y.
Fang X.-H.
Wang S. 
Wu Y.-C.
Keywords: DNA
messenger RNA
protein XAF1
tumor marker
unclassified drug
messenger RNA
signal peptide
tumor marker
tumor protein
XAF1 protein, human
cancer patient
cancer prognosis
DNA methylation
down regulation
human cell
human tissue
major clinical study
protein expression
reverse transcription polymerase chain reaction
stomach cancer
tumor recurrence
Western blotting
gene expression regulation
middle aged
promoter region
Stomach Neoplasms
tumor cell line
tumor volume
Biomarkers, Tumor
Cell Line, Tumor
DNA Methylation
Gene Expression Regulation, Neoplastic
Intracellular Signaling Peptides and Proteins
Middle Aged
Neoplasm Proteins
Neoplasm Recurrence, Local
Promoter Regions, Genetic
RNA, Messenger
Stomach Neoplasms
Tumor Burden
Issue Date: 2013
Citation: Ling Z.-Q., Lv P., Lu X.-X., Yu J.-L., Han J., Ying L.-S., Zhu X., Zhu W.-Y., Fang X.-H., Wang S., Wu Y.-C. (2013). Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer. PLoS ONE 8 (6) : e67195. ScholarBank@NUS Repository.
Abstract: Background:Methylated DNA in fluids may be a suitable biomarker for cancer patients. XAF1 has been shown to be frequently down-regulated in human gastric cancer (GC). Here, we investigated if XAF1 methylation in GC could be a useful biomarker.Methods:Real-time RT-PCR was used to detect XAF1 mRNA expression; immunohistochemistry and western blot were used to examine XAF1 protein expression in GC tissues (n = 202) and their corresponding para-cancerous histological normal tissues (PCHNTs). Real-time methylation specific-PCR was used to investigate XAF1 promoter methylation in the same panel of GC tissues, their PCHNTs and sera.Results:We confirmed frequent XAF1 down-regulation in both mRNA and protein levels in GC tissues as compared to normal controls and PCHNTs. XAF1 hypermethylation was evidenced in 83.2% (168/202) of GC tissues and 27.2% (55/202) of PCHNTs, while no methylation was detected in the 88 normal controls. The methylation level in GC tissues was significantly higher than that in PCHNTs (p<0.05). The hypermethylation of XAF1 significantly correlated with the down-regulation of XAF1 in GC tissues in both mRNA and protein levels (p<0.001 each). Moreover, we detected high frequency of XAF1 methylation (69.8%, 141 out of 202) in the sera DNAs from the same patients, while the sera DNAs from 88 non-tumor controls were negative for XAF1 methylation. The XAF1 methylation in both GC tissues and in the sera could be a good biomarker for diagnosis of GC (AUC = 0.85 for tissue and AUC = 0.91 for sera) and significantly correlated with poorer prognosis (p<0.001). In addition, after-surgery negative-to-positive transition of XAF1 methylation in sera strongly associated with tumor recurrence.Conclusions:1) Dysfunction of XAF1 is frequent and is regulated through XAF1 promoter hypermethylation; 2) Detection of circulating methylated XAF1 DNAs in the serum may be a useful biomarker in diagnosis, evaluating patient's outcome (prognosis and recurrence) for GC patients. © 2013 Ling et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0067195
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