title: Circulating MACC1 transcripts in colorectal cancer patient plasma predict metastasis and prognosis.
abstract: BACKGROUND
  Metastasis is the most frequent cause of treatment failure and death in colorectal cancer. Early detection of tumors and metastases is crucial for improving treatment strategies and patient outcome. Development of reliable biomarkers and simple tests routinely applicable in the clinic for detection, prognostication, and therapy monitoring is of special interest. We recently identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for colon cancer metastasis and allows identification of high-risk subjects in early stages, when determined in patients' primary tumors. To overcome the limitation of a restricted number of molecular analyses in tumor tissue, the establishment of a non-invasive blood test for early identification of high-risk cancer patients, for monitoring disease course and therapy response is strongly needed.
  
  
  RESULTS
  For the first time, we describe a non-invasive assay for quantification of circulating MACC1 transcripts in blood of more than 300 colorectal cancer patients. MACC1 transcript levels are increased in all disease stages of the cancer patients compared to tumor-free volunteers. Highest MACC1 levels were determined in individuals with metastases (all P<0.05). Importantly, high MACC1 levels correlate with unfavorable survival (P<.0001). Combining MACC1 with circulating transcripts of the metastasis gene S100A4, a transcriptional target of the Wnt/β-catenin-pathway, improves survival prediction for newly diagnosed cancer patients.
  
  
  CONCLUSIONS
  This blood-based assay for circulating MACC1 transcripts, which can be quantitated on a routine basis, is clinically applicable for diagnosis, prognosis, and therapeutic monitoring of cancer patients. Here we demonstrate the diagnostic and prognostic value of circulating MACC1 transcripts in patient plasma for metastasis and survival. Since MACC1 represents a promising target for anti-metastatic therapies, circulating MACC1 transcripts may prove to be an ideal read-out for monitoring therapeutic response of future interventions targeting MACC1-induced metastasis in cancer patients.
authors.affiliation: Experimental and Clinical Research Center, Charité University Medicine Berlin, at the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. ustein@mdc-berlin.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stein
authors.forename: Susen
authors.initials: S
authors.lastname: Burock
authors.forename: Pia
authors.initials: P
authors.lastname: Herrmann
authors.forename: Ina
authors.initials: I
authors.lastname: Wendler
authors.forename: Markus
authors.initials: M
authors.lastname: Niederstrasser
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schlag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000097:blood; D018709:Statistics, Nonparametric; D015534:Trans-Activators; D014157:Transcription Factors / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C544162:MACC1 protein, human; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C077591:S100A4 protein, human