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Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer.

Authors
Wong, JC; Chan, SK; Schaeffer, DF; Sagaert, X; Lim, HJ; Kennecke, H; Owen, DA; Suh, KW; Kim, YB; Tai, IT
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 17(12):4167-4176, 2011
Journal Title
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN
1078-0432
Abstract
PURPOSE: 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.



EXPERIMENTAL DESIGN: 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.
MeSH terms
AdultAgedAged, 80 and overCell Line, TumorColonic Neoplasms/*diagnosis/genetics/mortality/pathologyDown-RegulationGene Expression Profiling*Gene Expression Regulation, NeoplasticHCT116 CellsHumansMaleMatrix Metalloproteinase 1/antagonists & inhibitors/genetics/*metabolismMatrix Metalloproteinase 2/antagonists & inhibitors/genetics/*metabolismMiddle AgedNeoplasm Invasiveness/geneticsNeoplasm StagingPrognosisRectal Neoplasms/*diagnosis/genetics/mortality/pathologyRecurrenceSurvival AnalysisTissue Array AnalysisTreatment Outcome
DOI
10.1158/1078-0432.CCR-10-1224
PMID
21531813
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
AJOU Authors
서, 광욱김, 영배
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