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Gastric Cancer
Published in: Gastric Cancer 4/2015

01-10-2015 | Original Article

A novel splice variant of XIAP-associated factor 1 (XAF1) is expressed in peripheral blood containing gastric cancer-derived circulating tumor cells

Authors: Keiichi Hatakeyama, Yushi Yamakawa, Yorikane Fukuda, Keiichi Ohshima, Kanako Wakabayashi-Nakao, Naoki Sakura, Yutaka Tanizawa, Yusuke Kinugasa, Ken Yamaguchi, Masanori Terashima, Tohru Mochizuki

Published in: Gastric Cancer | Issue 4/2015

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Abstract

Background

XIAP-associated factor 1 (XAF1) is ubiquitously expressed in normal tissues, but its suppression in cancer cells is strongly associated with tumor progression. Although downregulation of XAF1 is observed in tumors, its expression profile in the peripheral blood of cancer patients has not yet been investigated. Here, we identified a novel XAF1 splice variant in cancer cells and then investigated the expression level of this variant in peripheral blood containing gastric cancer-derived circulating tumor cells (CTCs).

Methods

To identify splice variants, RT-PCR and DNA sequencing were performed in mRNAs extracted from many cancer cells. We then carried out quantitative RT-PCR to investigate expression in peripheral blood from all 96 gastric cancer patients and 22 healthy volunteers.

Results

The XAF1 variant harbored a premature termination codon (PTC) and was differentially expressed in highly metastatic cancer cells versus the parental cells, and that nonsense-mediated mRNA decay (NMD) was suppressed in the variant-expressing cells. Furthermore, splice variants of XAF1 were upregulated in peripheral blood containing CTCs. In XAF1 variant-expressing patients, the expression levels of other NMD-targeted genes also increased, suggesting that the NMD pathway was suppressed in CTCs.

Conclusions

Our study identified a novel splice variant of XAF1 in cancer cells. This variant was regulated through the NMD pathway and accumulated in NMD-suppressed metastatic cancer cells and peripheral blood containing CTCs. The presence of XAF1 transcripts harboring the PTC in the peripheral blood may be useful as an indicator of NMD inhibition in CTCs.
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Metadata
Title
A novel splice variant of XIAP-associated factor 1 (XAF1) is expressed in peripheral blood containing gastric cancer-derived circulating tumor cells
Authors
Keiichi Hatakeyama
Yushi Yamakawa
Yorikane Fukuda
Keiichi Ohshima
Kanako Wakabayashi-Nakao
Naoki Sakura
Yutaka Tanizawa
Yusuke Kinugasa
Ken Yamaguchi
Masanori Terashima
Tohru Mochizuki
Publication date
01-10-2015
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 4/2015
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-014-0426-3

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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