Circulating biomarkers in hepatocellular carcinoma

Morris, Karen; Tugwood, Jonathan; Khoja, Leila; Lancashire, Matthew; Szczepaniak-Sloane, Robert; Burt, Deborah J.; Shenjere, Patrick; Zhou, Cong; Hodgson, Clare; Ohtomo, Toshihiko; Katoh, Atsuhiko; Ishiguro, Takahiro; Valle, Juan W; Dive, Caroline

doi:10.1007/s00280-014-2508-7

Cited by 61 publications

(58 citation statements)

References 30 publications

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“…Much of the previously published literature on the use of the ISET device in detecting supposed CTCs using morphological criteria has found higher numbers of CTCs than are detected by epithelial antigens across a range of cancer types, despite larger size criteria [11–14, 17–19]. These studies have identified ‘CTCs’ by a range of cell and nuclear morphological criteria unlike the standard epithelial-marker based approaches (Table 5).…”

Section: Discussionmentioning

confidence: 99%

Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

et al. 2017

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IntroductionGiven the current postulated plasticity between epithelial and mesenchymal states of migratory cancer cells the detection of non-epithelial CTCs is an important scientific and clinical goal.MethodsWe used the filtration-based ISET technology to enrich circulating tumour cells (CTCs) in early breast cancer blood samples and identify them using a morphology-based immunocytochemistry (ICC) approach.ResultsWe found greater numbers of putative CTCs by this approach than by the cytokeratin-based CellSearch technology, but a high number of CTC false positives were identified in healthy volunteer samples which were not reduced in successive blood draws. Preliminary work using an oestrogen receptor (ER)-based multiplex ICC method in metastatic breast cancer ISET samples indicated a low number of ER+ CTCs even at this advanced stage.ConclusionsThis work highlights the challenges in enumerating CTCs without conventional epithelial markers.

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Section: Discussionmentioning

confidence: 99%

Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

et al. 2017

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“…The first application of the ISET method to detect CTCs in HCC patients was reported by Vona et al in 2000 [36]. The authors considered the ISET technique to provide a unique opportunity for the cytological analysis of peripheral blood in oncology and for combining immunomorphological studies with novel assays to explore genetic abnormalities in individual isolated cells [37]. The CanPatrol CTC analysis platform (SurExam, China) is another enrichment technique for CTC isolation and characterization [38, 39].…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Han

et al. 2018

J Exp Clin Cancer Res

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Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

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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%

“…4E). RRs for Serum AFP level were available in 8 studies [24,27,30,31,34,37,40,42]. The estimated pooled RRs indicated that CTC was associated with AFP≥400 ng/mL (RR 2.05, …”

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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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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Circulating biomarkers in hepatocellular carcinoma

Abstract: This is the first study to detect GPC3-positive CTCs in HCC, important for drug development with this target. The significant association of circulating CK18 with OS in HCC further exemplifies the utility of circulating biomarkers in cancer.

Cited by 61 publications

References 30 publications

Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

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

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