Correlation Of IGF-IR And Lin28B Protein Expression With Invasion And Metastasis Of Colorectal Cancer

Background and ObjectiveOver the past decade, incidence and mortality rates of colorectal cancer have a obvious upward trend. Colorectal cancer has become the world's third most common cancer. At present, surgery, chemotherapy, and radiotherapy are the major therapeutic remedies. However, the therapeutic effect is not satisfactory. The main reason of patients with poor prognosis and low 5-years survival rate after surgery is invasion and metastasis of tumor' cells. Therefore, it is significant to explore the molecular mechanisms of invasion and metastasis of colorectal cancer.Insulin-like growth factor receptor(IGF-IR) is a transmembrane heterotetrameric, belongs to receptor tyrosine kinase family, when the IGF-IR binding to its ligand, two major signaling pathways are activited, namely the phosphoinositide 3 kinase (PI3K)/Akt pathway and mitogen-activated protein kinase (MAPK) pathway. A great deal of studies have shown that the high expression of IGF-IR in many kinds of tumor tissues and is related to the carcinogenesis, development, invasion and metastasis of tumor. In recent years, the research of the contribution and mechanism between IGF-IR and colorectal cancer have been a hot spot. Another factor related to invasion and metastasis of colorectal cancer is Lin28B. Lin28B is a kind of RNA-binding protein. It can inhibit the maturation of tumour suppressor miRNAs let-7, in order to promote proliferation of tumor cells.IGF-IR comprises three let-7 binding sites, researches has shown that Lin28B can increase the expression of IGF-IR by inhibiting the let-7 binding sites. However, the expression of IGF-IR and Lin28B and their correlation in colorectal cancer are poorly reported.In order to provide new ideas and methods for colorectal cancer diagnosis and treatment, we detected the expression of IGF-IR and Lin28B in cancer tissues, neighboring normal tissues of colorectal cancer patients, and analyzed the relationship between the expression of IGF-IR and Lin28B and the clinic pathologic factors. Pertinence analysis are also conducted to explore the relation between IGF-IR and Lin28B in colorectal cancer tissues.Methods1.90 cases of colorectal cancer specimens of paraffin which confirmed by pathology after surgery in the Second Affiliated Hospital of Dalian Medical University blocks for the experimental group, divided into three groups, called without metastasis group, lymph node metastasis group and liver metastasis group (30 cases in every group). In addition,10 cases normal tissues greater than 5cm adjacent to the tumor tissue were selected as the control group. All specimens were recorded with detailed basic information, TNM stage, degree of differentiation, lymph node metastasis and distant metastasis.2. The expression of IGF-IR and Lin28B in colorectal cancer tissue and normal colorectal tissue adjacent to the cancer are detected by immunohistochemistry.3. SPSS 17.0 software was adopted to analyze the experimental data, ?2 test was used to compare the positive rate. Spearman rank correlation test was adopted to analyze the relationship between the expression of IGF-IR and Lin28B.Results1. The positive rates of IGF-IR and Lin28B in colorectal cancer tissue were significantly higher than those in the normal colorectal tissue adjacent to the cancer (P< 0.05).2. The positive rates of IGF-IR and Lin28B in colorectal cancer tissues with lymphatic metastasis were significantly higher than those in the tissues of non-metastatic cancers (P<0.05). The positive rates of IGF-IR and Lin28B in colorectal cancer tissues with liver metastases were significantly higher than those in the tissues of non-metastatic cancers (P<0.05). The overexpression of IGF-IR and Lin28B was significantly related with the tumor TNM stage (P<0.05)3. There are no significant associations between IGF-IR and Lin28B expression and clinic pathologic factors including tumor size, location, depth of invasion, differentiation, gross type, and the patient's age, gender (P> 0.05)4. The IGF-IR expression correlated positively with the Lin28B expression in colorectal cancer tissues (P< 0.05).Conclusions:1. The expression of IGF-IR and Lin28B in colorectal cancer is higher than the adjacent normal tissues, suggesting that IGF-IR and Lin28B may related to the formation of colorectal cancer.2. The study find out the positive association between the expression of IGF-IR and Lin28B and lymph node metastasis, liver metastasis, TNM stage in colorectal carcinoma tissues, suggesting that IGF-IR, Lin28B may participate in the development, invasion and metastasis of colorectal cancer,.3. Expression of IGF-IR and Lin28B in colorectal cancer was positively correlated, indicating IGF-IR and Lin28B may play a cooperative role in the carcinogenesis, development, invasion and metastasis of colorectal cancer.4. In summary, IGF-IR and Lin28B is expected to become a new target for tumor-targeted therapy.