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Series GSE112679 Query DataSets for GSE112679
Status Public on Aug 07, 2019
Title Genome-wide Mapping of 5-Hydroxymethylcytosines in Circulating Cell-free DNA as a Non-invasive Approach for Early Detection of Hepatocellular Carcinoma
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Background: The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC.

Methods: Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2,554 Chinese subjects: 1,204 HCC patients, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC), and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularization for feature selection.

Results: The 5hmC-Seal data from HCC patients showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer (BCLC) staging system from non-HCC (validation set: AUC = 88.4%; 95% CI, 85.8-91.1%), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumors (e.g., ≤ 2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC = 84.6%; 95% CI, 80.6-88.7%), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (e.g., smoking/alcohol intake history).

Conclusions: We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
 
Overall design Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2,554 Chinese subjects: 1,204 HCC patients, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC), and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularization for feature selection.
 
Contributor(s) Cai J, Chen L, Zhang Z, Zhang X, Lu X, Liu W, Shi G, Yang G, Gao P, Yang Y, Ke A, Xiao L, Dong R, Zhu Y, Yang X, Wang J, Zhu T, Yang D, Huang X, Sui C, Qiu S, Shen F, Sun H, Zhou W, Zhou J, Nie J, Chang Z, Stroup EK, Zhang X, Brian CC, Wan Yee L, He C, Wang H, Zhang W, Fan J
Citation(s) 31358576
Submission date Apr 04, 2018
Last update date Aug 07, 2019
Contact name Zhou Zhang
E-mail(s) zhou.zhang@northwestern.edu
Organization name Northwestern University
Department Preventive Medicine
Street address 680 North Lake Shore Drive, Suite 1400
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (2606)
GSM3076193 blood_1
GSM3076194 blood_2
GSM3076195 blood_3
Relations
BioProject PRJNA448890
SRA SRP137706

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Supplementary file Size Download File type/resource
GSE112679_RAW.tar 264.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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