Expression Of DOC2, Rasp21 And C-Fos Proteins In Colorectal Carcinoma Tissue And Their Clinical Significance

Background and ObjectivesThe colorectal cancer is one of the most common gastrointestinal tumors.With the changing habit of people's life in recent years, the incidence of colorectal cancer in China shows an upward trend.At present,the most effective treatment is still surgical removal of tumor as much as possible.Colorectal cancer is always diagnosed in advanced stage because there is no symptom in early period.The majority of patients die of local recurrence or distant metastasis although the primary tumor has been resected.The survival rate of colorectal cancer is greatly related to lymph node and distant metastasis. However,the formation mechanism of the metastasis is not yet very clear.Although the comprehensive.treatment effect of colorectal cancer has been made great progress in recent years,the treatment effect of patients with metastasis is still not optimistic. Early diagnosis and anticipation the risk of metastasis are very critical to improve the prognosis of colorectal cancer patients. So,it is very important for us to find a meaningful pathology indicators which can indicate the evolution and prognosis of colorectal cancer.Along with the development of science and technology,more and more people recognize that the occurrence of colorectal cancer is a multi-stage,multi-step,complex process and is related to abnormal changes of multiple genes.The Human DOC2 belongs to Disabled gene family,which is also named the Dab2.DOC2/Dab2's structure suggest that it may be a signal molecule,which can not only regulate the growth and differentiation,but also have the function of tumor suppression.The specific mechanism of DOC2/Dab2 is not entirely clear,so the tumor suppressor gene has not yet formed a conclusion.Oncogene has become a hotspot in recent years.Ras genes are more closely-watched cancer gene in current study,the activation of which is closely related with a variety of tumor.RasP21 is most closely related to the occurrence of colorectal cancer.lt not only participates in cell malignant transformation through abnormal signal transduction,but also plays an important role in tumor angiogenesis.So,the role of Ras and its related signal transduction pathways are worthy of further study in colorectal cancer genesis and development.C-Fos is a kind of nuclear fission signal effector protein,which not only plays an important regulatory role in cell proliferation and growth,but also regulates the transcription of multiple genes.The expression and regulation of c-Fos is closely related with the occurrence and development of many diseases.So,in this study we investigate the expression of DOC2/Dab2,rasP21,c-Fos in colorectal cancer and their relationship with clinicopathological parameters in the development process of colorectal cancer. These provide a valuable clinicopathological indicators and new ideas to develop the new tumor target therapy.Materials and Methods1.110 cases of colorectal carcinoma tissue,29 cases of colorectal adenoma tissue and 40 cases of para-carcinoma normal mucosa tissue were collected. Any chemotherapy, radiotherapy and other biological targeted therapy have never been carried out in all cases before surgery.2. The expression of DOC2/Dab2,rasP21 and c-Fos proteins were detected by immunohistochemistry.The correlation among the three indicators and their correlations to the clinicopathologic parameters of colorectal carcinoma were analyzed,and the interaction of the three indicators were explored in colorectal cancer.3. Statistical analysis,SPSS 13.0 software was used for statistical analysis.Chi-square test or Fisher's exact test of probabilities were used to analyze the date.The correlation of DOC2/Dab2,rasP21 and c-Fos was analyzed with Spearman rank correlation.Test leve a=0.05.Results1. Immunohistochemistry results showed:the positive staining of DOC2/Dab2 protein in colorectal tissue was located in the cytoplasm.The positive expression rates of DOC2/Dab2 protein in para-carcinoma normal colorectal tissue, colorectal adenoma and colorectal carcinoma were 82.50%(33/40),55.17%(16/29) and 30.91% (34/110),the difference among the three groups was statistically significant(P <0.05),and statistical difference was also get from the two inter-group comparisons(P <0.017).The expression level of DOC2/Dab2 protein in colorectal carcinoma showed no significant relation between age,sex,histology type,differentiated degree,invasion depth and clinical stage (P>0.05).But in the research we revealed that the expression level was significantly concerned with lymph node and liver metastasis(P<0.05).2. Immunohistochemistry results showed:the positive staining of rasP21 protein in colorectal tissue was located in the cellular membrane or cytoplasm.The positive expression rates of rasP21 protein in para-carcinoma normal colorectal tissue, colorectal adenoma and colorectal carcinoma were 7.50%(3/40),58.62%(17/29)and 68.18%(75/110),and the difference among the three groups was statistically significant(P<0.05).The expression of rasP21 protein in colorectal carcinoma and colorectal adenoma tissures was significantly higher than the normal colorectal mucosa(P<0.05),but there was no significant difference between the former two groups.The expression level of rasP21 protein in colorectal carcinoma showed no significant relation between age,sex,histology type,invasion depth and clinical stage(P>0.05).But in the research we found that the expression level was significantly correlated with differentiated degree, lymph node and liver metastasis (P<0.05).3. Immunohistochemistry results showed:the positive staining of c-Fos protein in colorectal tissue was located in the cellular nucleus or cellular cytoplasm.The positive expression rates of c-Fos protein in para-carcinoma normal colorectal tissue, colorectal adenoma and colorectal carcinoma were 12.50%(5/40),37.93%(11/29) and 55.45%(61/110),and the difference among the three groups was statistically significant(P<0.05).The expression of c-Fos protein in colorectal carcinoma and colorectal adenoma tissues was significantly higher than the normal colorectal mucosa(P<0.05),but there was no significant difference between the former two groups.The expression level of c-Fos protein in colorectal carcinoma showed no significant relation between age, sex, histology type, invasion depth, clinical stage, lymph node and liver metastasis (P>0.05).But the research revealed that the expression level was significantly concerned with differentiated degree (P<0.05).4. In colorectal carcinoma there was a negative correlation between the expression of DOC2/Dab2 and rasP21 proteins (P＜0.05).5. In colorectal carcinoma there was a negative correlation between the expression of DOC2/Dab2 and c-Fos proteins (P<0.05).6. In colorectal carcinoma there was a positive correlation between the expression of rasP21 and c-Fos proteins (P＜0.05).Conclusions1. The expression of DOC2/Dab2 protein in normal colorectal,adenoma and carcinoma present a degraded trend.In colorectal carcinoma the expression of DOC2/Dab2 protein is significantly correlated with lymph node and liver metastasis. In the process of colorectal carcinogenesis,the down-regulated of DOC2/Dab2 protein is an early event,which probably promote the metastasis of colorectal carcinoma.2. The expression of rasP21 protein in colorectal carcinoma and adenoma tissues is significantly higher than that in the normal colorectal mucosa tissue.In colorectal carcinoma the expression of rasP21 protein is significantly correlated with differentiation degree,lymph node and liver metastasis.The abnormal expression of rasP21 protein may be correlated with the tumorigenesis and development of colorectal tissue,which probably promote the invasion and metastasis of this disease.3. The expression of c-Fos protein in colorectal carcinoma and adenoma tissues is significantly higher than that in the normal colorectal mucosa tissue.In colorectal carcinoma the expression of c-Fos protein is significantly correlated with differentiation degree.The high expression of c-Fos protein is probably an early molecular event in the process of colorectal tumorigenesis and development.4. In colorectal carcinoma,the expression of DOC2/Dab2 protein is negative correlation with rasP21 and c-Fos proteins.They participate in colorectal tumorigenesis,development,invasion and metastasis via opposite mechanism of action.5. In colorectal carcinoma,the expression of rasP21 and c-Fos proteins present positive correlation and synergism.They may both participate in the process of colorectal carcinogenesis and development.