Abnormal expression of TRIB3 in colorectal cancer: a novel marker for prognosis.
BACKGROUND
TRIB3 is a human homologue of Drosophila tribbles. Previous studies have shown that TRIB3 controls the cell growth through ubiquitination-dependent degradation of other proteins, whereas its significance in the prognosis of colorectal cancer (CRC) is not yet fully understood.


METHODS
This study comprised 202 patients who underwent surgery for CRC, as well as 22 cell lines derived from human gastrointestinal cancer. The correlation of gene expression with clinical parameters in patients was assessed. The biological significance was evaluated by knockdown experiments in seven colorectal cancer cell lines.


RESULTS
A total of 20 cancer cell lines (90.9%) expressed the TRIB3 gene. The assessment in surgical specimens indicated that the gene expression was significantly higher in the cancerous region than in the marginal non-cancerous region. Patients with high TRIB3 expression were statistically susceptible to a recurrence of the disease, and showed poorer overall survival than those with low expression. The assessment of TRIB3 knockdown in five cell lines showed that small interfering RNA (siRNA) inhibition resulted in a statistically significant reduction in cell growth.


CONCLUSIONS
These data strongly suggest the usefulness of TRIB3 as a marker for predicting the prognosis of CRC patients, showing a basis for the development of effective treatments for CRC.
Miyoshi
N
N
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan.
Ishii
H
H
Mimori
K
K
Takatsuno
Y
Y
Kim
H
H
Hirose
H
H
Sekimoto
M
M
Doki
Y
Y
Mori
M
M
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases