TY - JOUR
T1 - Gene expression profiling of primary and metastatic colon cancers identifies a reduced proliferative rate in metastatic tumors
AU - Ganepola, Ganepola A.P.
AU - Mazziotta, Robert M.
AU - Weeresinghe, Dilendra
AU - Corner, Georgia A.
AU - Parish, Cheryl J.
AU - Chang, David H.
AU - Tebbutt, Niall C.
AU - Murone, Carmel
AU - Ahmed, Naseem
AU - Augenlicht, Leonard H.
AU - Mariadason, John M.
N1 - Funding Information:
been supported and funded by NIH grant CA123316; and The Valley Hospital, Ridgewood, New Jersey.
PY - 2010/1
Y1 - 2010/1
N2 - The objective of this study was to gain insights into the biological basis of the metastatic process by characterizing the gene expression differences between primary and metastatic colon cancers. Recent studies have demonstrated that few new mutational changes are acquired during the metastatic progression of colon tumors [Jones et al., Proc Natl Acad Sci USA 105 (11): 4283-4288, 2008]. However, the extent to which epigenetic and transcriptional changes occur between primary and metastatic colon cancer remains unknown. We approached these issues using Affymetrix microarrays to assess the similarities and differences in gene expression profiles between macro-dissected primary and metastatic colon tumors. Unexpectedly, we found that expression of a number of cell proliferation markers were reduced in the liver metastases of colon tumors when compared to primary tumors. This finding was validated by immunohistochemical staining of Ki67 and Cyclin D1 in Formalin-Fixed Paraffin-Embedded (FFPE) section of the same samples, and in an independent cohort of FFPE matched tumor and metastatic tissue samples. These results indicate that significant transcriptional differences exist between primary and metastatic colon tumors, and demonstrate that metastatic lesions have a lower proliferative rate compared to primary tumors. These findings may have implications for interpreting differences in response rates between primary and metastatic lesions and suggest that measurement of expression-based biomarkers in metastatic tissue will be most informative for understanding the basis of response of metastatic tumors to therapeutic intervention.
AB - The objective of this study was to gain insights into the biological basis of the metastatic process by characterizing the gene expression differences between primary and metastatic colon cancers. Recent studies have demonstrated that few new mutational changes are acquired during the metastatic progression of colon tumors [Jones et al., Proc Natl Acad Sci USA 105 (11): 4283-4288, 2008]. However, the extent to which epigenetic and transcriptional changes occur between primary and metastatic colon cancer remains unknown. We approached these issues using Affymetrix microarrays to assess the similarities and differences in gene expression profiles between macro-dissected primary and metastatic colon tumors. Unexpectedly, we found that expression of a number of cell proliferation markers were reduced in the liver metastases of colon tumors when compared to primary tumors. This finding was validated by immunohistochemical staining of Ki67 and Cyclin D1 in Formalin-Fixed Paraffin-Embedded (FFPE) section of the same samples, and in an independent cohort of FFPE matched tumor and metastatic tissue samples. These results indicate that significant transcriptional differences exist between primary and metastatic colon tumors, and demonstrate that metastatic lesions have a lower proliferative rate compared to primary tumors. These findings may have implications for interpreting differences in response rates between primary and metastatic lesions and suggest that measurement of expression-based biomarkers in metastatic tissue will be most informative for understanding the basis of response of metastatic tumors to therapeutic intervention.
KW - Gene expression of colon tumor
KW - Gene expression profiling
KW - Immunohistochemical validation
KW - Metastatic colorectal cancer
KW - Metastatic process
KW - Metastatic proliferation
KW - Microarray analysis of colon cancer
KW - Primary and metastatic colon cancer
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U2 - 10.1007/s10585-009-9295-2
DO - 10.1007/s10585-009-9295-2
M3 - Article
C2 - 19882219
AN - SCOPUS:74849137748
SN - 0262-0898
VL - 27
SP - 1
EP - 9
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -