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Review
. 2014 Mar 28;20(12):3265-86.
doi: 10.3748/wjg.v20.i12.3265.

Liquid biopsy of gastric cancer patients: circulating tumor cells and cell-free nucleic acids

Masahiro Tsujiura  1 , Daisuke Ichikawa  1 , Hirotaka Konishi  1 , Shuhei Komatsu  1 , Atsushi Shiozaki  1 , Eigo Otsuji  1
Affiliations
Review

Liquid biopsy of gastric cancer patients: circulating tumor cells and cell-free nucleic acids

Masahiro Tsujiura et al. World J Gastroenterol. .

Abstract

To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called "liquid biopsy", would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of "tailor-made" cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.

Keywords: Biomarker; Cell-free nucleic acids; Circulating tumor cells; Gastric cancer; Liquid biopsy; MicroRNA.

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Figures

Figure 1
Figure 1
Flow chart of current and potential applications of circulating tumor cell and circulating cell-free nucleic acids technologies. Circulating tumor cells (CTCs): The blood samples from cancer patients are processed through various isolation/enrichment and detection techniques. A new in vivo approach allows the enrichment of CTCs directly from a peripheral vein of patients, using a wire functionalized by attachment of epithelial cell adhesion antibodies[32]. CTCs are usually captured along with contaminating leukocytes. Various detection methods are utilized to detect the rare cell population in the bloodstream. Circulating cell-free nucleic acids (cfNAs): Plasma/serum are generally isolated with centrifuge techniques and subsequently processed for the extraction of specific nucleic acids. Cancer-specific alterations are most commonly analyzed in circulating DNA. Circulating miRNA has attracted increasing attention because of its stability in plasma/serum. Most recently, long non-coding RNA in plasma was also evaluated as a potent biomarker in gastric cancer patients. CGH: Comparative genome hybridization; FACS: Fluorescence activated cell sorter; FISH: Fluorescence in situ hybridization; FAST: Fiberoptic array scanning technology; EPISPOT: Epithelial immunospot; qRT-PCR: Quantitative real-time polymerase chain reaction; LOH: Loss of heterozygosity.
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