Expression of oncofetal RNA-binding protein CRD-BP/IMP1 predicts clinical outcome in colon cancer.
The oncofetal CRD-BP/IMP1 RNA binding protein regulates posttranscriptionally a handful of RNA transcripts, implicated in cell adhesion and invadopodia formation and was recently identified as a target of the beta-catenin/Tcf transcription factor that is constitutively activated in colorectal carcinomas (CRCs). The expression of CRD-BP/IMP1 was studied in normal adult intestines and CRCs. In normal mucosa, CRD-BP/IMP1 immunoreactivity was observed in few scattered cells located predominantly at or near the bottom of the crypts, whereas in CRCs the protein was detectable in tumor cells of 50% of the specimens analyzed. CRD-BP/IMP1 mRNA expression was measured by qRT-PCR in 78 CRCs. Thirty-two (41%) of the specimens were negative or had negligible expression, whereas the remaining forty-six (59%) expressed a wide range of CRD-BP/IMP1 mRNA levels. CRD-BP/IMP1 mRNA expression correlated with that of the putative stem/progenitor cell marker Musashi-1 mRNA (p = 0. 035). CRD-BP/IMP1 positive tumors metastasized and/or recurred more frequently (p = 0.001) and its expression defined a group of patients with shorter survival (p = 0.014). Furthermore, in a multivariate analysis CRD-BP/IMP1 expression was found to be an independent predictor of survival (p = 0.015). For stage I & II patients, the differences in metastasis/recurrence and survival rates remained significant (p = 0.001 and 0.033, respectively). These findings indicate that CRD-BP/IMP1 positive tumors exhibit early disease dissemination and unfavorable prognosis.
Dimitriadis
Euthymios
E
Department of Genetics, Saint Savvas Oncological Hospital, Athens, Greece.
Trangas
Theoni
T
Milatos
Stavros
S
Foukas
Periklis G
PG
Gioulbasanis
Ioannis
I
Courtis
Nelly
N
Nielsen
Finn C
FC
Pandis
Nikos
N
Dafni
Urania
U
Bardi
Georgia
G
Ioannidis
Panayotis
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C406144:IGF2BP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins