Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets

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http://hdl.handle.net/10138/298096

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Agarwal , R , Narayan , J , Bhattacharyya , A , Saraswat , M & Tomar , A K 2017 , ' Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets ' , Cancer Genetics , vol. 216 , pp. 37-51 . https://doi.org/10.1016/j.cancergen.2017.06.002

Title: Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets
Author: Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar
Contributor: University of Helsinki, Medicum
Date: 2017-10
Language: eng
Number of pages: 15
Belongs to series: Cancer Genetics
ISSN: 2210-7762
URI: http://hdl.handle.net/10138/298096
Abstract: A very low 5-year survival rate among hepatocelluHar carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TOGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy.
Subject: Hepatocellular carcinoma
kinases
mRNA expression
subtype classification
survival analysis
MESSENGER-RNA EXPRESSION
RECEPTOR 4
SPINDLE CHECKPOINT
SIGNALING PATHWAY
CANCER GROWTH
INHIBITION
BIOMARKERS
IDENTIFICATION
METHYLATION
RESISTANCE
3122 Cancers
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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