DAPK1 as an independent prognostic marker in liver cancer

Ling Li, Libin Guo, Qingshui Wang, Xiaolong Liu, Yongyi Zeng, Qing Wen, Shudong Zhang, Hang Fai Kwok, Yao Lin, Jingfeng Liu

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    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.

    LanguageEnglish
    Article numbere3568
    Number of pages1
    JournalPeerJ
    Volume2017
    Issue number7
    DOIs
    Publication statusPublished - 1 Jan 2017

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    Death-Associated Protein Kinases
    liver neoplasms
    Liver Neoplasms
    protein kinases
    Liver
    death
    Genes
    Messenger RNA
    Catenins
    Proteins
    genes
    protein synthesis
    Negative Staining

    Keywords

    • DAPK1
    • IHC
    • Liver cancer
    • Prognosis
    • Survival

    Cite this

    Li, L., Guo, L., Wang, Q., Liu, X., Zeng, Y., Wen, Q., ... Liu, J. (2017). DAPK1 as an independent prognostic marker in liver cancer. PeerJ, 2017(7), [e3568]. https://doi.org/10.7717/peerj.3568
    Li, Ling ; Guo, Libin ; Wang, Qingshui ; Liu, Xiaolong ; Zeng, Yongyi ; Wen, Qing ; Zhang, Shudong ; Kwok, Hang Fai ; Lin, Yao ; Liu, Jingfeng. / DAPK1 as an independent prognostic marker in liver cancer. In: PeerJ. 2017 ; Vol. 2017, No. 7.
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    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.",
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    author = "Ling Li and Libin Guo and Qingshui Wang and Xiaolong Liu and Yongyi Zeng and Qing Wen and Shudong Zhang and Kwok, {Hang Fai} and Yao Lin and Jingfeng Liu",
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    Li, L, Guo, L, Wang, Q, Liu, X, Zeng, Y, Wen, Q, Zhang, S, Kwok, HF, Lin, Y & Liu, J 2017, 'DAPK1 as an independent prognostic marker in liver cancer', PeerJ, vol. 2017, no. 7, e3568. https://doi.org/10.7717/peerj.3568

    DAPK1 as an independent prognostic marker in liver cancer. / Li, Ling; Guo, Libin; Wang, Qingshui; Liu, Xiaolong; Zeng, Yongyi; Wen, Qing; Zhang, Shudong; Kwok, Hang Fai; Lin, Yao; Liu, Jingfeng.

    In: PeerJ, Vol. 2017, No. 7, e3568, 01.01.2017.

    Research output: Contribution to journalArticle

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    AU - Li, Ling

    AU - Guo, Libin

    AU - Wang, Qingshui

    AU - Liu, Xiaolong

    AU - Zeng, Yongyi

    AU - Wen, Qing

    AU - Zhang, Shudong

    AU - Kwok, Hang Fai

    AU - Lin, Yao

    AU - Liu, Jingfeng

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    AB - 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.

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    Li L, Guo L, Wang Q, Liu X, Zeng Y, Wen Q et al. DAPK1 as an independent prognostic marker in liver cancer. PeerJ. 2017 Jan 1;2017(7). e3568. https://doi.org/10.7717/peerj.3568