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DAPK1 as an independent prognostic marker in liver cancer
Li, Ling1,2; Guo, Libin3,4; Wang, Qingshui3,4; Liu, Xiaolong2; Zeng, Yongyi2; Wen, Qing5; Zhang, Shudong6; Kwok, Hang Fai3; Lin, Yao4; Liu, Jingfeng1,2
2017-07-19
Source PublicationPEERJ
ISSN2167-8359
Volume5
Abstract

The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002) and overall survival (p = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

KeywordLiver Cancer Ihc Survival Dapk1 Prognosis
DOIhttp://doi.org/10.7717/peerj.3568
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000406373400005
PublisherPEERJ INC
The Source to ArticleWOS
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorKwok, Hang Fai; Lin, Yao; Liu, Jingfeng
Affiliation1.Hepatopancreatobiliary Surgery Department, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
2.United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
3.Faculty of Health Sciences, University of Macau, Taipa, Macau
4.College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province, China
5.Centre for Cancer Research & Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom
6.Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, Londonderry, United Kingdom
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Li, Ling,Guo, Libin,Wang, Qingshui,et al. DAPK1 as an independent prognostic marker in liver cancer[J]. PEERJ,2017,5.
APA Li, Ling.,Guo, Libin.,Wang, Qingshui.,Liu, Xiaolong.,Zeng, Yongyi.,...&Liu, Jingfeng.(2017).DAPK1 as an independent prognostic marker in liver cancer.PEERJ,5.
MLA Li, Ling,et al."DAPK1 as an independent prognostic marker in liver cancer".PEERJ 5(2017).
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