Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

Background/Aims: The prognostic value of circulating tumor cells (CTC) detected in hepatocellular carcinoma (HCC) patients is currently under debate. We conducted a meta-analysis of available studies to assess its prognostic value for patients diagnosed with HCC. Methods: Medline, Ovid Database, Embase, The Science Citation Index, and Cochrane library, search was conducted on all studies reporting the outcomes of interest. The studies were set up according to the inclusion/exclusion criteria. Using a random-effects model, meta-analysis was performed using hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) as effect measures. Heterogeneity of the studies was tested for each pooled analysis. Subgroup and sensitivity analyses were also performed. Results: twenty-three published studies that matched the selection criteria were included in this meta-analysis. CTC positivity was significantly associated with Relapse free survival (RFS) (HR 3.03, 95% CI: [1.89-4.86]; p<0.00001) and Overall survival (OS) (HR 2.45, 95% CI: [1.73-3.48]; p<0.00001). CTC positivity were also significantly associated with TNM Stage (RR 1.30, 95% CI: [1.02-1.65]; p=0.03), Tumor size (RR 1.36, 95% CI: [1.09-1.69]; p=0.006), Vascular invasion (RR 1.99, 95% CI: [1.43-2.77]; p<0.0001), Portal vein tumor thrombus (RR 1.73, 95% CI: [1.42-2.11]; p=0.0001), Serum alpha-fetoprotein (AFP) level (RR 2.05, 95% CI: [1.18-3.54]; p=0.01). Conclusion: CTC positivity indicates poor prognosis in patients with hepatocellular carcinoma, and associated with poor clinicopathologic parameters.

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“…9 studies [22,28,31,[38][39][40][41][42][43] (Fig. 4B), the between-study heterogeneity was moderate (I 2 =33%, p = 0.16).…”

Section: Correlation Of Circulating Tumor Cells With Clinicopathologimentioning

confidence: 99%

Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis

Fan

Yang

Yuan

et al. 2015

Cell Physiol Biochem

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“…An increasing number of studies have shown that CD90, which is expressed by hepatic stem/progenitor cells during liver development, could be used as a marker for human LCSCs and as a target for the diagnosis and therapy of hepatocellular carcinoma (HCC). [10][11][12] Therefore, CD90 + LCSCs are referred to as CD90 + LCSCs in this study. Relapse and metastases can occur if the applied treatments fail to remove cancer stem cells (CSCs); therefore, therapies that eliminate CSCs may be more effective than current drugs that target proliferating non-CSCs in the treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

Yang¹,

Tang²,

Miao³

et al. 2015

IJN

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Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90 + LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90 + LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90 + LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90 + LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90 + LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90 + LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.

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“…Recently, the CD90 stem cell marker has been identified as a prognostic marker for high-grade gliomas, and CD44 has been shown to be a potential metastatic marker [28, 29]. Bahnassy and colleagues [30] have shown that aberrant expression of cancer stem cell markers (CD133, CD90 and CD44) contributes to tumor progression. In fact, according to our in vivo results, the CD133+/CD90+/CD44+ tumor stem cells may be responsible for dissemination of glioblastoma, which leads to reduced patient survival [30].…”

Section: Discussionmentioning

confidence: 99%

“…Bahnassy and colleagues [30] have shown that aberrant expression of cancer stem cell markers (CD133, CD90 and CD44) contributes to tumor progression. In fact, according to our in vivo results, the CD133+/CD90+/CD44+ tumor stem cells may be responsible for dissemination of glioblastoma, which leads to reduced patient survival [30]. The glioblastoma CD133 + cells also co-express significant levels of SSEA-3 (stage-specific embryonic antigen 3), Mush-1 (neural stem cell marker) and Nanog (transcriptional regulator involved proliferation and self-renewal of embryonic stem (ES) cells).…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

et al. 2016

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Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types.

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Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

Abstract: CTC counts and AFP, CK19, telomerase, and MAGE1/MAGE3 expression predict disease progression in patients with HCV, whereas telomerase, MAGE3, CD90, CD133 and CK19 are prognostic markers in HCC.

Cited by 37 publications

References 32 publications

Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis

Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

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