Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer
- Equal contributors
1 Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China
2 Department of Surgery, Pudong New Area People's Hospital, Shanghai, China
3 Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
4 Department of Surgery, First Affiliated Hospital of Soochow University, Suzhou, China
5 Department of Internal Medicine, University of Michigan, Ann Arbor, USA
BMC Cancer 2010, 10:184 doi:10.1186/1471-2407-10-184Published: 7 May 2010
Insulin-like growth factor-I receptor (IGFIR) has been shown to regulate the tumor development. The objective of the current study is to determine the association of IGFIR with lymph node metastasis and to explore the related mechanism in human colorectal cancer in clinic.
In a random series of 98 colorectal cancer patients, the expressions of IGFIR, vascular endothelial growth factor (VEGF) and VEGF-C were investigated by immunohistochemistry, and the association of these expressions with lymph node metastasis was statistically analyzed. The expressions of VEGF and VEGF-C in colorectal cancer cells stimulated with IGF-I were also examined by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.
Higher rates of IGFIR (46%), VEGF (53%), and VEGF-C (46%) expression were found in colorectal cancer tissues than in normal and colorectal adenoma tissues. These expressions were significantly associated with clinicopathologic factors and lymph node status. We also found the concomitant high expressions of IGFIR/VEGF (P < 0.001) and IGFIR/VEGF-C (P = 0.001) had a stronger correlation with lymph node metastasis than did each alone or both low expressions. In addition, IGF-I could effectively induce the VEGF and VEGF-C mRNA expression and protein secretion in colorectal cancer cells expressing IGFIR molecules. Moreover, Patients who had strong staining for IGFIR, VEGF and VEGF-C showed significantly less favorable survival rates compared with patients who had low staining for these molecules (P < 0.001). The survival rates of patients who were both high expression of IGFIR/VEGF and IGFIR/VEGF-C also were significantly lower compared with patients who were negative or one of high expression of these molecules (P < 0.001).
Together the findings indicated for the first time that simultaneous examination of the expressions of IGFIR, VEGF and VEGF-C will benefit the diagnosis of lymph node metastasis in order to assay the prognosis and determine the treatment strategy in patients with colorectal cancer undergoing surgery.