Meta-Analysis: Prognostic Value of Survivin in Patients with Hepatocellular Carcinoma

Liu, Jin Long; Zhang, Xue Jun; Zhao, Zhanzheng; Zhang, An Hong; Wang, Wei; Dong, Jia Hong

doi:10.1371/journal.pone.0083350

Cited by 28 publications

(21 citation statements)

References 36 publications

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“…One possible reason may be the lack of information on the molecular heterogeneity of the tumors being treated and consequently, making it difficult to interpret the overall biological response. Over-expression of survivin in HCC has been reported to correlate with poor prognosis [14]. In this study, we hypothesized that targeting survivin could be a treatment strategy for HCC and subsequently demonstrated the remarkable heterogeneity of expression of survivin and its phosphorylated active form (p-survivin) in HCC patients' tissues and cell lines.…”

Section: Introductionmentioning

confidence: 90%

The over-expression of survivin enhances the chemotherapeutic efficacy of YM155 in human hepatocellular carcinoma

et al. 2015

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The inability of chemotherapeutic drugs to selectively target HCC tumor cells because of their predominant resistant phenotype to most conventional anticancer agents bestows a major obstacle for the clinical management of HCC. In this report, we have examined and demonstrated the remarkable heterogeneity of expression of survivin and its phosphorylated active form (p-survivin) in HCC patients' tissues and cell lines. Furthermore, the expression of survivin and p-survivin in HCC cell lines was found to be associated with response to the small-molecule survivin suppressant YM155. Therefore, in the HCC cell lines that express elevated level of survivin and p-survivin, YM155 efficiently inhibited their proliferation, induced cell cycle arrest and apoptosis resulting in DNA damage through the dysregulation of cell-cycle checkpoint-related regulatory genes. Importantly, YM155 yielded significantly better therapeutic effect than sorafenib when tested in an orthotopic mouse model using patient-derived HCC xenografts with elevated survivin and p-survivin expression. Our results clearly demonstrated that the level of survivin and p-survivin expression could serve as molecular predictive biomarkers to select potential YM155-responsive patients, in a move towards delivering precision medicine for HCC patients.

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Section: Introductionmentioning

confidence: 90%

The over-expression of survivin enhances the chemotherapeutic efficacy of YM155 in human hepatocellular carcinoma

et al. 2015

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“…First, an interruption of survivin levels plays an important role in reducing apoptosis of HCC. In agreement with this, several studies have concluded that survivin expression was correlated with poor prognosis in patients with HCC, and upregulation of survivin is an independent risk factor in hepatocellular carcinoma cell survival as well as in resistance to apoptosis (33). Second, and most importantly, survivinT34A increases arsenic trioxide-induced apoptosis.…”

Section: Discussionmentioning

confidence: 54%

SurvivinT34A increases the therapeutic efficacy of arsenic trioxide in mouse hepatocellular carcinoma models

et al. 2016

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Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions. Disruption of survivin by the plasmid encoding the phosphorylation-defective mouse survivin threonine 34→alanine mutant (Msurvivin T34A plasmid) has proved a promising strategy for suppressing a variety of murine cancer. In the present study, we attempted to test Msurvivin T34A and arsenic trioxide (ATO) on a cell line and mice bearing subcutaneous tumors, with regard to their effects and mechanisms. We observed that the co-treatment with surivinT34A and ATO significantly enhanced the antitumor activity by induction of apoptosis in Hepa1-6 tumor cells in vitro, compared with control groups. The synergistic apoptosis-inducing effect of combination of these two drugs resulted in elevation of reactive oxygen species (ROS) level which could be antagonized by the antioxidant N-acetyl-l-cysteine. The combination treatment induced ROS-dependent collapse of the mitochondrial membrane potential. Moreover, the tumor growth in vivo was also remarkably inhibited by combination of surivinT34A and ATO when compared with control groups. Our findings demonstrate that the combination of surivinT34A and ATO exerted synergistic antitumor effects, providing a new perspective for clinical treatment of HCC.

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“…Yu, et al found that the expression of BIRC5 was increased in LIHC tissues as compared to those adjacent nontumor samples and non-cancerous liver tissues (Yang et al 2011). Several articles demonstrated that BIRC5 expression correlated with unfavorable clinicopathological characteristics and predicted poor survivals in patients with LIHC (Augello et al 2009;Liu et al 2013;Ye et al PeerJ reviewing PDF | (2016:09:13329:1:1:NEW 5 Feb 2017)…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma (v0.1)"

2017

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Background. Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. Methods. Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values. Results. A list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, 'pathways in cancer', was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95%CI: 0.982-0.998, P<0.001, sensitivity: 96.0%, specificity: 96.5%). BIRC5 (P=0.021) and CCNE1 (P=0.027) were associated with poor prognosis, while CDKN2A (P=0.066) and E2F1 (P=0.088) demonstrated no statistically significant differences. Discussion. The study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, 'pathways in cancer'. The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be further investigated given its high evidence level of diagnosis, whereas the prognostic powers of BIRC5 and CCNE1 are equally attractive and worthy of attention.

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Meta-Analysis: Prognostic Value of Survivin in Patients with Hepatocellular Carcinoma

Cited by 28 publications

References 36 publications

The over-expression of survivin enhances the chemotherapeutic efficacy of YM155 in human hepatocellular carcinoma

The over-expression of survivin enhances the chemotherapeutic efficacy of YM155 in human hepatocellular carcinoma

SurvivinT34A increases the therapeutic efficacy of arsenic trioxide in mouse hepatocellular carcinoma models

Peer Review #1 of "From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma (v0.1)"

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