title: Circulating Metastasis Associated in Colon Cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Susen
authors.initials: S
authors.lastname: Burock
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Herrmann
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Wendler
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Niederstrasser
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.affiliation: Susen Burock, Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000097:blood; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C544162:MACC1 protein, human; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C077591:S100A4 protein, human
keywords: Circulating transcripts; Diagnosis; Gastric cancer; MACC1; Plasma; Prognosis; S100A4; Survival