Increased LEF1 expression and decreased Notch2 expression are strong predictors of poor outcomes in colorectal cancer patients.
OBJECTIVE
We aimed to examine the expression of lymphoid enhancer factor 1 (LEF1) and Notch2 in colorectal cancer (CRC) and their association with clinicopathologic variables and CRC patients' prognosis.


METHODS
Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to assess the expression of LEF1 and Notch2 in 184 patients with CRC.


RESULTS
We observed a strong negative correlation between LEF1 expression and Notch2 expression (P < 0.001). Both LEF1 mRNA and protein expression increased while the Notch2 mRNA and protein expression decreased in tumor specimens compared with the matched paratumorous normal tissue (P < 0.001). An increase in LEF1 protein expression was significantly associated with lymph node metastases, distant metastasis, advanced TNM (tumor-node-metastasis) stage, and shorter overall survival. A decrease in Notch2 protein expression was associated with poorly differentiated tumors, lymph node metastases, distant metastasis, advanced TNM stage, and shorter overall survival of patients. In the multivariate Cox regression analysis, the LEF1 protein expression (P < 0.001), Notch2 protein expression (P < 0.001), TNM stage (P < 0.001), and the combination of increased LEF1 protein coexpression and decreased Notch2 protein coexpression (P < 0.001) were found to be independent prognostic indicators in CRC.


CONCLUSIONS
Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients.
Department of Oncology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Wen-Juan
WJ
Wang
Yu
Y
Yao
Li-Li
LL
Jiang
Ting-Hua
TH
Hu
Jie-Qun
JQ
Ma
Zhi-Ping
ZP
Ruan
Tao
T
Tian
Hui
H
Guo
Shu-Hong
SH
Wang
Ke-Jun
KJ
Nan
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C497764:NOTCH2 protein, human; D012333:RNA, Messenger; D051883:Receptor, Notch2