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Application of capillary electrophoresis for the early diagnosis of cancer

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Abstract

Early diagnosis is the key to the effective treatment of cancer. The detection of cancer biomarkers plays a critical role not only in cancer early diagnosis, but also in classification and staging tumor progression, or assessment prognosis and treatment response. Currently, various molecular diagnostic techniques have been developed for cancer biomarker studies, with many of the more effective approaches requiring a separation step before detection. Capillary electrophoresis (CE) can perform rapid and efficient separation with small samples, which is well-suited for analysis of both small- and macro- molecule biomarkers in complex samples. CE has different separation modes and can couple to different detectors into a variety of platforms, such as conducting studies on DNA/ RNA point mutation, protein misexpression, and metabolite abnormality. Similarly, microchip capillary electrophoresis (MCE) appears as a very important biomarker screening platform with the merits of high throughput, integration, and miniaturization, which makes it a promising clinical tool. By hyphenated different detectors, or integrated with immunoassay, PCR/LDR and related technologies, MCE can be constructed into diverse platforms used in genomics, proteomics, and metabolomics study for biomarkers discovery. The multiplex biomarker screening approach via CE- or MCE-based platforms is becoming a trend. This paper focuses on studies of cancer biomarkers via CE/MCE platforms, based on the studies published over the past 3 years. Some recent CE applications in the field of cancer study, such as cancer theranostics, are introduced.

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Abbreviations

5-hmC:

5-hydroxymethylcytosine

5-hmdC:

5-hydroxymethyl-2′-deoxycytidine

AFP:

alpha-fetoprotein

AGP:

alpha-1-acid glycoprotein

APC:

adenomatous polyposis coli

BCAA:

branched-chain amino acid

bp:

base pair

CE:

capillary electrophoresis

CFLDR:

continuous-flow ligase detection reaction

CFPCR:

continuous-flow polymerase chain reaction

CGE:

capillary gel electrophoresis

CSCE:

conformation-sensitive capillary electrophoresis

CTC:

circulating tumor cell

CTC:

circulating tumor cell

CZE:

capillary zone electrophoresis

DAD:

diode array detector

DHPLC:

denaturing high performance liquid chromatography

dLIF:

dual-laser-induced fluorescence

EMC:

enzyme mismatch cleavage

EMMA:

enhanced mismatch mutation analysis

ESI:

electrospray ionization

FDA:

Food and Drug Administration (US)

FITC:

fluorescein isothiocyanate

FRET:

fluorescence resonance energy transfer

Hp:

haptoglobin phenotype

IA:

immunoassay

ICP:

inductively coupled plasma

LDR:

ligase detection reaction

LEDIF:

light-emitting diode-induced fluorescence

LIF:

laser-induced fluorescence

LOD:

limit of detection

microTAS:

micro-total-analysis systems

miRNA:

microRNA

MMR:

mismatch repair

MRB:

moving reaction boundary

MRP:

multidrug resistance-associated protein

MS:

mass spectrometry

MSI:

microsatellite instability

MT:

metallothionein

NASH:

non-alcoholic steatohepatitis

NGS-CE:

non-gel sieving -capillary electrophoresis

NIH:

National Institute of Health (US)

PAGE:

polyacrylamide gel electrophoresis

PCa:

prostate cancer

PCR:

polymerase chain reaction

PSA:

prostate-specific antigen

REF:

restriction endonuclease fingerprinting

RFLP:

restriction fragment length polymorphism

SDS:

sodium dodecyl sulfate

SSCP:

single strand conformation polymorphism

SYBR green 1:

a flourescence dye for dsDNA

TGCE:

temperature gradient capillary electrophoresis

TOF:

time-of-flight

UV:

ultraviolet

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Acknowledgments

The authors thank Stephanie Baker at the University of Illinois at Urbana-Champaign and Qiang Gao at Dali University for their contributions to the manuscript.

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Yang, Z., Sweedler, J.V. Application of capillary electrophoresis for the early diagnosis of cancer. Anal Bioanal Chem 406, 4013–4031 (2014). https://doi.org/10.1007/s00216-014-7722-y

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