Abstract
Background/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. Conclusion. Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients.
Highlights
Over the last few decades, a significant decline in cancerrelated mortality of colorectal cancer (CRC) has been observed due to the considerable progress in the diagnosis and treatment, but CRC still remains a major public health problem throughout the world
Significant differences in lymphoid enhancer factor-1 (LEF1) expression in tumor tissue were observed between tumors with node metastasis, distant metastasis and different TNM stages (P = 0.001,
Our results showed that LEF1 mRNA was significantly increased in most CRC tissues compared with the paratumorous normal colorectal tissues (P < 0.001), and the association between LEF1 mRNA expression and clinicopathologic factors was in accordance with the results of the immunohistochemical analysis (Table 2)
Summary
Over the last few decades, a significant decline in cancerrelated mortality of colorectal cancer (CRC) has been observed due to the considerable progress in the diagnosis and treatment, but CRC still remains a major public health problem throughout the world. The Wnt and Notch signaling pathways have been shown to play a major role in intestinal morphogenesis and homeostasis [4,5,6,7]. Several members of the Wnt signaling pathway, either tumor suppressors APC and Axin or oncogene β-catenin and lymphoid enhancer factor-1 (LEF1), are often aberrantly activated in CRC development [9]. Transcription factor LEF1 is a potential candidate biomarker for CRC since it serves as a key role in the regulation of many important cellular functions, including proliferation [11], growth [12], survival [13], mobility [14], and angiogenesis [15]
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