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Circulating Tumor Cells (Liquid Tumor Biopsy) in Hepatocellular Carcinoma: Biology, Methodologies, and Clinical Implications

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Part of the book series: Current Clinical Oncology ((CCO))

Abstract

Hepatocellular carcinoma (HCC) is among the most aggressive of cancers, and the prognosis remains poor. Data are accumulating that circulating tumor cells (CTCs) are an active source of recurrence or metastasis in HCC patients. As a novel biomarker for the metastatic disease process, CTC study has become a very active field of research. As for the detection of CTCs in HCC patients, some interesting and encouraging results have currently been obtained although the knowledge about their clinical relevance is lagging behind other major cancers. This chapter describes recent discoveries related to the biology of CTCs, outlines their potential clinical utility as a real-time liquid tumor biopsy, reviews current advances in different techniques or strategies available for their detection and isolation, and introduces progress obtained from clinical studies on detection and molecular characterization of CTCs and circulating cancer stem cells (CCSCs) in HCC patients and current challenges.

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Abbreviations

aCGH:

Array comparative genomic hybridization

AFP:

Alpha-fetoprotein

Akt:

Protein kinase B

ASGPR:

Asialoglycoprotein receptor

BCLC:

Barcelona clinic liver cancer

bFGF:

Basic fibroblast growth factor

CAM:

Collagen adhesion matrix

CCSCs:

Circulating cancer stem cells

CEA:

Carcinoembryonic antigen

CGH:

Comparative genomic hybridization

CICs:

Cancer-initiating cells

CKs:

Cytokeratins

CPS1:

Carbamoyl phosphate synthetase 1

CSCs:

Cancer stem cells

CT:

Computer tomography

CTCs:

Circulating tumor cells

CTM:

Circulating tumor microemboli

DAPI:

Dye 4′,6-diamidino-2-phenylindole

ECM:

Extracellular matrix

EDTA:

Ethylene diamine tetraacetic acid

EGF:

Epidermal growth factor

ELISPOT:

Enzyme-linked immunospot assay

EMT:

Epithelial–mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

EPISPOT:

Epithelial immunospot

ERK:

Extracellular signal-regulated kinase

FACS:

Fluorescence-activated cell sorting

FDA:

Food and Drug Administration

FISH:

Fluorescence in situ hybridization

GFP:

Green fluorescent protein

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HER2:

Human epidermal growth factor receptor-2

IGFBP1:

Insulin-like growth factor-binding protein 1

IL-6:

Interleukin-6

IL-8:

Interleukin-8

ISET:

Isolation by size of epithelial tumor cells

MACS:

Magnetic activated cell sorting

MET:

Mesenchymal–epithelial transition

MICs:

Metastasis-initiating cells

MRI:

Magnetic resonance imaging

mTOR:

Mammalian target of rapamycin

PBMCs:

Peripheral blood mononuclear cells

PET:

Positron emission tomography

PI3K:

Phosphoinositide 3-kinase

PSA:

Prostate-specific antigen

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

PVTT:

Portal vein tumor thrombus

RBCs:

Red blood cells

RFS:

Recurrence-free survival

SNP:

Single nucleotide polymorphisms

TACE:

Transcatheter arterial chemoembolization

TERT:

Telomerase reverse transcriptase

TNM:

Tumor-node-metastasis

WBCs:

White blood cells

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Acknowledgments

The work was supported by grants from the China National Key Projects for Infectious Disease (No. 2012ZX10002012-10) and the National Nature Science Foundation of China (No. 81172207, 81272669, and 81201721).

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Correspondence to Zhengfeng Yin .

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Yin, Z. (2016). Circulating Tumor Cells (Liquid Tumor Biopsy) in Hepatocellular Carcinoma: Biology, Methodologies, and Clinical Implications. In: Carr, B. (eds) Hepatocellular Carcinoma. Current Clinical Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-34214-6_12

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