Gene expression profiling: canonical molecular changes and clinicopathological features in sporadic colorectal cancers.
OBJECTIVE
To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment.


METHODS
Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction (RT-PCR).


RESULTS
The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair (MMR) defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis (P < 0.001). Amongst 47 differentially expressed genes, seven (PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS) were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory.


CONCLUSIONS
We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.
Kim
Jin-Cheon
JC
Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 388-1 Poongnap-2-Dong Songpa-Ku, Seoul 138-736, South Korea. jckim@amc.seoul.kr
Kim
Seon-Young
SY
Roh
Seon-Ae
SA
Cho
Dong-Hyung
DH
Kim
Dae-Dong
DD
Kim
Jeong-Hyun
JH
Kim
Yong-Sung
YS
D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017491:Genes, APC; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics
D051153:Wnt Proteins