Expression of selenium-binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer.
To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
Li
Tianhong
T
Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA. tli@montefiore.org
Yang
Wancai
W
Li
Maomi
M
Byun
Do-Sun
DS
Tong
Chang
C
Nasser
Shannon
S
Zhuang
Min
M
Arango
Diego
D
Mariadason
John M
JM
Augenlicht
Leonard H
LH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics; D051137:Selenium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017741:Survivors
D034741:RNA, Small Interfering; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins