Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 333-341
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.333
Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker
Susen Burock, Pia Herrmann, Ina Wendler, Markus Niederstrasser, Klaus-Dieter Wernecke, Ulrike Stein
Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany
Pia Herrmann, Ulrike Stein, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Ina Wendler, Markus Niederstrasser, Charité University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany
Klaus-Dieter Wernecke, Institute of Medical Biometry, Charité University Medicine Berlin, Luisenstraße 65, 10117 Berlin, Germany
Author contributions: Burock S and Stein U designed the concept of the study; Herrmann P performed qRT-PCR; Burock S, Herrmann P, Wendler I and Stein U analyzed the data; Burock S, Niederstrasser M and Wernecke KD performed statistical analyses; Burock S and Stein U wrote the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ulrike Stein, Professor, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany. ustein@mdc-berlin.de
Telephone: +49-30-94063432 Fax: +49-30-94062780
Received: March 21, 2014
Peer-review started: March 23, 2014
First decision: April 2, 2014
Revised: May 5, 2014
Accepted: July 22, 2014
Article in press: July 22, 2014
Published online: January 7, 2015
Processing time: 291 Days and 17.6 Hours
Abstract

AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer patients.

METHODS: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients, either newly diagnosed with gastric cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well as follow-up patients. Findings were controlled by using plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR.

RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumor-free volunteers and gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage, compared to tumor-free volunteers: patients with tumors without metastasis (P = 0.005), with synchronous metastasis (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival when compared with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore, gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated (P = 0.001).

CONCLUSION: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study.

Keywords: Gastric cancer; Plasma; Circulating transcripts; MACC1; S100A4; Diagnosis; Prognosis; Survival

Core tip: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer Metastasis Associated in Colon Cancer 1 (MACC1) in a prospective study of gastric cancer patients. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We discriminated tumor-free volunteers and gastric cancer patients (all P < 0.001, sensitivity 0.68 (95%CI: 0.45-0.85), specificity 0.89 (95%CI: 0.77-0.95) of each disease stage (P < 0.05 for each). Shorter survival correlated with high circulating MACC1 transcript levels (P = 0.0015). Thus, circulating MACC1 transcript levels in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival.