Expression And Clinical Significance Of Mcm7, Mcm5 And Cyclin E Protein In Rectal Carcinoma

Background and ObjectivesThe colorectal carcinoma (CRC)is a common malignant neoplasm in digestive tract, which includes colonic carcinoma and rectal carcinoma. With improving the life quality and the changing habit of people's life in recent years, the incidence and mortality of colorectal carcinoma in China shows an upward trend. At present,the most effective treatment is still surgical removal of tumor as much as possible.But, not all sufferers can cut off with the surgical operation, because tumor stage is crucial to effect of surgical remove. Always,patients of the colorectal carcinoma are diagnosed in advanced stage because there is no symptom in early period. The majority of these patients die of local recurrence or distant metastasis although the primary tumor has been removed. The Survival Time of colorectal carcinoma is greatly related to lymph node and distant metastasis. However,the formation mechanism of the metastasis is not yet very doubtless.Although the comprehensive treatment effect of colorectal carcinoma 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 important to improve the prognosis of colorectal carcinoma patients.So,it is very crucial for us to find a meaningful pathology indicators which can indicate the evolution and prognosis of colorectal carcinoma. The rectum cancer has the big fraction of the colorectal carcinoma,and the aim of this study is to look for pathology indicators which indicate the evolution and prognosis of rectum carcinoma.Along with the development of science and technology, people recognize that lots of biological molecules are associated with the occurrence and development of colorectal carcinoma. These molecules provide important insight into diagnosis and prognosis and may be looked as new tumor markers,such as mcm7,mcm5 etc. Mcm7, mcm5 belong to the family of Minichromosome Maintenance proteins,which includes the six proteins mcm2 through mcm7. The mcm2-7 proteins appear to form hetero-hexamers and play important roles in initiation and elongation during DNA replication.They participate in many of the pathophysiology processes,such as cell cycle control, abnormal cellular proliferation, tumorigenesis and so on. In initiation and elongation during DNA replication, the mcm protein can ensure that the genome was replicated once and only once in each cell cycle. The result of disorder of DNA replication will result in the instability of the genome, normal cellular malignancy transformation and malignant tumor development. In recent years, MCM proteins have become a hotspot in all over the world. Molecular researchs show that MCM proteins can reflects cell's multiplication situation sensitively and specially.They are better than PCNA,Ki-67 and very meaningful in prediction malignant degree, proliferative degree and prognosis of the tumor.At the same time, the increasing of MCM is not only predicting the proliferation of malignant cell, but also atypical cells of undetermined significance.The aim of this study is to investigate the expression of mcm7, mcm5,cyclin E in colorectal cancer and their relationship with clinicopathological parameters in the development process of rectal cancer. These will provide valuable clinicopathological indicators and new ideas to develop the new tumor target therapy.Materials and Methods1.104 cases of rectal adenocarcinoma tissue,28 cases of rectal adenoma tissue and 36 cases of para-carcinoma normal mucosa tissue were collected from First Hospital Affiliated to Zhengzhou University. Any chemotherapy, radiotherapy and other biological targeted therapy have never been carried out in all cases before surgery.2. The expression of mcm7,mcm5 and cyclin E proteins were detected by SP immunohistochemistry.The correlation among the three indicators and their correlations to the clinicopathologic parameters of rectal adenocarcinoma were analyzed,and the significance of the three indicators were explored in rectal cancer.3. Statistical analysis,SPSS 17.0 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 mcm7,mcm5 and cyclin E proteins were analyzed with Spearman rank correlation.Test leverα=0.05.Results1. Immunohistochemistry results showed:the positive staining of mcm7 and mcm5 protein in rectal tissue was mainly located in the cellular nucleus.The positive expression rates of mcm7 protein in para-carcinoma normal rectal tissue, rectal adenoma and rectal adenocarcinoma were 27.78% (10/36), 53.57%(15/28) and 82.69%(86/104), 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<0.05).The positive expression rates of mcm5 protein in para-carcinoma normal rectal tissue, rectal adenoma and rectal adenocarcinoma were 22.22%(8/36),42.86%(12/28) and 76.92% (80/104), 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 <0.05).The expression level of mcm7 and mcm5 protein in rectal adenocarcinoma showed no significant relation between age,sex, and size of the tumor. (P>0.05).But in the research we revealed that the expression level was significantly concerned with degree of differentiation, invasive depth,lymph node and stage of the tumor(P<0.05).2. Immunohistochemistry results showed:the positive staining of cyclin E protein in rectal tissue was mainly located in the cellular cytoplasm and nucleus.The positive expression rates of cyclin E protein in para-carcinoma normal rectal tissue, rectal adenoma and rectal adenocarcinoma were 11.11%(4/36),28.57% (8/28) and 67.31%(70/104), 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<0.05).The expression level of cyclin E protein in rectal adenocarcinoma showed no significant relation between age,sex, size and invasive depth of the tumor. (P>0.05).But in the research we revealed that the expression level was significantly concerned with degree of differentiation, lymph node and stage of the tumor (P<0.05).3. In rectal adenocarcinoma, there was a positive correlation between the expression of mcm7, mcm5 and cyclin E proteins (P<0.05).Conclusions1. The expression of mcm7 and mcm5 protein in normal rectal,adenoma and adenocarcinoma present a upgraded trend. In rectal adenocarcinoma, the expression of mcm7 and mcm5 protein is significantly correlated with degree of differentiation, invasive depth,lymph node and stage of the tumor. In the process of rectal carcinogenesis,the up-regulated of mcm7 and mcm5 protein is an early event,which probably promote the genesis,invasion and metastasis of rectal adenocarcinoma.2. The expression of cyclin E protein in normal rectal,adenoma and adenocarcinoma present a upgraded trend.In rectal adenocarcinoma, the expression of cyclin E protein is significantly correlated with degree of differentiation, lymph node and stage of the tumor. In the process of rectal carcinogenesis,the up-regulated of cyclin E protein is an early event,which probably promote the genesis and metastasis of rectal adenocarcinoma.3. In rectal carcinoma,the expression of mcm7,mcm5 and cyclin E proteins present positive correlation and synergism. They may all participate in the process of rectal carcinogenesis and development.4. Mcm7, mcm5 and cyclin E protein are possibly valuable biomolecules for diagnosis and prognosis of rectal adenocarcinoma.