Synchronous global assessment of gene and protein expression in colorectal cancer progression.
Well-established models of colorectal cancer progression are based on the idea that the disease evolves through a multistep process involving sequential genetic mutations, suggesting that progression through clinically defined stages should correlate with well-defined patterns of gene expression. The majority of studies to date, however, have assessed these processes one gene and one protein at a time. We report the first comprehensive assessment of both gene and protein expression performed in parallel across progressive stages of human colorectal neoplasia. Remarkably, despite the global nature of the gene expression assessment, very few genes could be linked with certainty to specific proteins through currently available annotations. Furthermore, the correlation of expression between identified genes and proteins was poor. Nevertheless, both produced expression signatures that differentiated normal mucosa and nonmalignant adenomas from each other and from the malignant carcinomas and both produced fairly consistent subclasses of the malignancies, suggesting that a molecular staging might be more appropriate provided that these profiles can be tied to clinical outcome. This is potentially important as clinical staging is widely used as a prognostic indicator and used in the decision to pursue adjuvant therapies.
Kwong
Ka Yin
KY
Mammalian Genomics, The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.
Bloom
Gregory C
GC
Yang
Ivana
I
Boulware
David
D
Coppola
Domenico
D
Haseman
Jeremy
J
Chen
Emily
E
McGrath
Andrew
A
Makusky
A James
AJ
Taylor
John
J
Steiner
Sandra
S
Zhou
Jeffery
J
Yeatman
Timothy J
TJ
Quackenbush
John
J
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics*; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D013058:Mass Spectrometry; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D025341:Principal Component Analysis; D011379:Prognosis; D040901:Proteomics; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D012333:RNA, Messenger; D012313:RNA