title: Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer.
abstract: OBJECTIVE
  Treatments for colorectal cancer (CRC) are primarily disease stage based. However, heterogeneity in outcome within even a single stage highlights its limitations in predicting disease behavior. Recently, the role of gene expression as predictive and prognostic markers has been explored. Our objectives were to identify consistently differentially expressed genes through meta-analysis of high-throughput gene-expression studies, and evaluate their predictive and prognostic significance in colon (CC) and rectal (RC) cancers.
  
  
  METHODS
  Publications applying high-throughput gene- expression technologies to specific CRC stages were identified. A vote counting strategy was used to identify the most significant differentially expressed genes. Their predictive and prognostic values were independently assessed in a tissue microarray of 191 cases of stage II-IV CC/RC from two tertiary care centers. Their biological effects were also examined in vitro.
  
  
  RESULTS
  MMP1 and MMP2 were identified as consistently underexpressed in liver metastasis compared with primary CRC. Shorter time to distant metastasis and overall survival occurred in stage III CC lacking MMP1 expression, and in stage III RC lacking MMP2. MMP1 levels in stage II and III CC were associated with increased likelihood of distant metastasis, whereas the risk of local recurrence in stage III RC could be stratified by MMP2. Promotion of cell invasion of CRC cell lines exposed to MMP1/2 inhibitors were confirmed in vitro.
  
  
  CONCLUSIONS
  MMP1 and MMP2 may be useful biomarkers that can help stratify patients at higher risk of developing recurrence in colorectal cancer, and guide individualized treatment decisions to achieve better outcomes.
authors.affiliation: Division of Gastroenterology, Department of Medicine, and Department of Pathology, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, Canada, V5Z 1M9.
authors.forename: John C T
authors.initials: JC
authors.lastname: Wong
authors.forename: Simon K
authors.initials: SK
authors.lastname: Chan
authors.forename: David F
authors.initials: DF
authors.lastname: Schaeffer
authors.forename: Xavier
authors.initials: X
authors.lastname: Sagaert
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Lim
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
authors.forename: David A
authors.initials: DA
authors.lastname: Owen
authors.forename: Kwang W
authors.initials: KW
authors.lastname: Suh
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Isabella T
authors.initials: IT
authors.lastname: Tai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012008:Recurrence; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1