DNA甲基化驱动的转录表达特征作为肝癌预后预测标志物的价值

doi:10.16288/j.yczz.20-139

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Hereditas(Beijing) ›› 2020, Vol. 42 ›› Issue (8): 775-787.doi: 10.16288/j.yczz.20-139

• Research Article • Previous Articles Next Articles

Prognostic and predictive value of a DNA methylation-driven transcriptional signature in hepatocellular carcinoma

Hongbo Luo¹, Pengbo Cao²(), Gangqiao Zhou^1,²()

^1. Guizhou University School of Medicine, Guiyang 550025, China
^2. State Key Lab of Proteomics, National Center for Protein Sciences (Beijing), Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;

Received:2020-05-18 Revised:2020-07-10 Online:2020-08-20 Published:2020-07-10
Contact: Cao Pengbo,Zhou Gangqiao E-mail:birchcpb@163.com;zhougq114@126.com
Supported by:
Supported by the National S&T Major Project Nos(2018ZX10732202);Supported by the National S&T Major Project Nos(2017ZX10203205)

Abstract

Abstract:

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. DNA methylation alterations are frequently observed in malignant tumours and play critical roles in the development of cancers, including HCC. To provide novel clinical prognosis biomarkers for HCC patients, we first performed a comprehensive analysis and identified a collection of prognosis-associated genes with DNA methylation-driven expression dysregulation in HCCs. Then, we optimally established a 10-gene prognostic risk score model using the least absolute shrinkage and selection operator (LASSO) analysis. Cox's proportional hazards regression analysis revealed that the high-risk score is significantly associated with poor prognosis after being adjusted by clinical parameters, indicating its potential prognostic value. The receiver operating characteristic curve (ROC) analysis showed that this 10-gene prognostic risk score model outperformed several other publicly available models in predicting both short- and long-term prognosis. Gene set enrichment analysis revealed that the high-risk score is relevantly associated with pathways involved in cell cycle and DNA damage repair. The above results indicate that we have constructed a 10-DNA-methylation-driven-gene prognostic risk score model, which might serve as a potential prognostic biomarker for HCC patients and guide treatment decisions for patients at high risk of tumour progression.

Key words: hepatocellular carcinoma, transcriptome, epigenome, prognostic model

Hongbo Luo, Pengbo Cao, Gangqiao Zhou. Prognostic and predictive value of a DNA methylation-driven transcriptional signature in hepatocellular carcinoma[J]. Hereditas(Beijing), 2020, 42(8): 775-787.

Figures/Tables 8

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研究队列	数据集	样本量	数据类型	数据来源
发掘队列	SRP069212	20例配对的癌和癌旁组织	mRNA表达	GEO
	SRP118972	12例癌组织样本和8例癌旁组织	mRNA表达	GEO
	GSE89852	33例配对的癌和癌旁组织	DNA甲基化	GEO
	GSE54503	66例配对的癌和癌旁组织	DNA甲基化	GEO
模型训练队列	TCGA-LIHC	371例癌组织和50例癌旁组织	mRNA表达和DNA甲基化	TCGA
模型训练队列	ICGC-LIRI-JP	203例癌组织	mRNA表达	ICGC
模型验证队列	GSE76427	115例癌组织	基因表达	GEO
模型验证队列	GSE84005	37例癌组织	基因表达	GEO

基因	HR (95% CI)	P值	LASSO系数	基因组变异频率(%)
CDCA8	2.21 (1.54~3.01)	<0.0001	0.1194	0.0
PRC1	1.85 (1.29~2.54)	0.0005	0.08869	0.3
MAPT	1.72 (1.21~2.46)	0.0021	0.2597	1.7
SFN	1.72 (1.21~2.45)	0.0021	0.001652	0.3
STC2	1.73 (1.22~2.43)	0.0021	0.03600	0.8
MYO18B	1.69 (1.19~2.37)	0.0031	0.1932	4.0
PBK	1.67 (1.17~2.35)	0.0036	0.06524	6.0
MAEL	1.55 (1.09~2.17)	0.013	-0.1766	10.0
TTC39A	1.55 (1.09~2.17)	0.013	-0.01347	1.4
LPL	1.55 (1.10~2.18)	0.014	0.003126	7.0

Prognostic and predictive value of a DNA methylation-driven transcriptional signature in hepatocellular carcinoma

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