Expression And Significance Of Cyclinb1, Cdc25b And P27 In Gastric Adenocarcinoma

The stomach cancinoma is malignant tumor,which is originated from the gastric mucosal epithelial cells,accounted for 95%of the malignant stomach tumor.The outbreak rate of stomach cancer is very high in our country,the death rate is the first of the malignant tumor,the average death rate of stomach cancer in our national is up to 20/100,000,and the rate in the male is higher than that in the female.The year outbreak rate of stomach cancer is 17.6/100,000 in the world.The outbreak rate in Japan,Denmark and etc.is high,however,that in the United States and Australia is lower.Some forelands in our country,such as Shandong,Zhejiang,Shanghai Fukien and etc.are the high deliver areas.Because the symptom of stomach cancer is much lightly in early stage,and no body to advertise for,it is usually neglect because of the difficulty for discover.Most of the stomach cancers have already belonged to a medium later period while usually it is discovered.Seeing from the histology,the great majority of stomach cancer is glandular cancer.Both normal cells and the cancer cells proliferate through the cell cycle,just the regulation of the cell cycle take place a change in the cancer cells.Therefore it have a necessity to study the outbreak mechanism of the gastric adenocarcinoma in the cell cycle further,understand the biological behaviors of the gastric adenocarcinoma,provide a help for instructing the clinical treatment.The control of the cell cycle is mainly through the common function of various cyclin(the cell cycle protein),CDK(the cyclin-dependent protein kinase) and CKI (the inhibitor of the CDK) to carry out.Cyclin,which is synthesizes continuously a backlog continuously in the cell period and the activity appear the periodic variety,is a set of protein with similar structure,known together as the cyclin family,currently have 8 kinds of members, named Cyclin A,B,C...H.Each kind of type has several isoforms.As regulatory subunit,they need to combine different catalytic subunit(cyclin-dependent protein kinase,CDK) to form the compound(cyclin-CDK),thus to modify the function protein phosphorily,and control the cell cycle to carry on.The CyclinB1 is one of the main components to control the cell cycle G₂/M restriction.CDC25(A,B and C) is a dual-specific phosphatase protein in the cell cycle to serve as an important role.CDC25B is the most important member of the CDC25 kinase family,through the various stages of the cell cycle,which exist in different location of cells at different phases of the cell cycle,and play a key role in the phases of the conversion ot the cell cycle,as the same important role in the process of mitotic cells.It is a major responsibility to activate CDK1-cyclinB,which is the start factor of the early mitotic cells,but also is the core of the control factor of resumption of oocyte meiosis.CDC25B is a phosphorylated protein,and the regulation of its activity is through phosphate and phosphoric acid.The conduct of excessive CDC25B can promote the growth of tumor and the malignant transformation of cells.The over-expression of gene may occur in the early stages of cancer,which causes abnormal gene expression of CDC25B,and promotes the occurrence of tumors.CKI is the inhibitor of the CDK,non-covalently combine with CDK to inhibit the activity of CDK,which is one of the important confrontation mechanisms involved in cell cycle inspection mechanism.The CKI of mammalian cells include Ink4(inhibitor of CDK4),Kip(kinase inhibition protein) and etc.,and Kip include p21,p27 and p57.P27 combine with cyclin-CDK to form complexes,the latter whether have the inhibition role depend largely on the quantity of P27,the so-called chemical dosage form to function,which is one of its characteristics.Another feature of P27 role is non-specificity,it can inhibit the activity of all CDK.P27 has a higher level in G₀-phase and decrease gradually from the G₀-phase to S-phase.P27 expression is induced mainly by stimulation.In this study,expression of cyclinB1,CDC25B and P27 in 15 cases of adjacent cancer tissue,45 cases of gastric adenocarcinoma tissue was detected by immunohistocal method.The relationship between the expression of the three protein in gastric adenocarcinomas and clinical pathological factors of gastric adenocarcinoma was analyzed.The correlation of the expression of the three proteins in gastric adenocarcinoma was also analyzed.Explore the roles of CyclinB1,CDC25Band P27 in the development of gastric adenocarcinoma and their prognostic values,provide a experimental basis for the gene therapy of gastric adenocarcinoma.Methods1.Immunohistochemical method was used to detect the protein expression of CyclinB1,CDC25B and P27 in 15 cases of adjacent cancer tissue,45 cases of gastric adenocarcinoma tissue.The relationship between protein expressions and clinicopathological features of gastric adenocarcinoma was analyzed accordingly. Besides,the correlations between the expression of CyclinB1,CDC25B and P27 were also analyzed.2.Statistical analysis:The SPSS13.0 statistical package program 10.0 was used for data analysis.Association between the variables was tested byχ²test and FISH exact probability method.The correlation analysis was analyzed by Spearman rank correlation,α=0.05 was deemed to a statistically significant test of the standard.Result1.The positive rates of CyclinB1 and CDC25B in gastric adenocarcinoma tissues were 80.0%(36/45) and 84.4%(38/45) respectively;both in adjacent cancer tissues were 13.3%(2/15).The positive rates of cyclinB1 and CDC25B in gastric adenocarcinoma tissues were significantly higher than those in adjacent cancer tissues(P＜0.05).2.The positive rate of p27 in adjacent cancer tissues and gastric adenocarcinoma tissue were 93.3%(14/15) and 22.2%(10/45) respectively.The difference in positive rates is statistically significant(P＜0.05). 3.The positive rates of CyclinB1and CDC25B in gastric adenocarcinoma tissues were not associated with the age,sex,clinical stage and lymph node metastasis(P＞0.05),but were significantly associated with histological grade(P＜0.05).The expression of P27 was not associated with the age,sex,histological grade and clinical stage(P＞0.05),but was significantly associated with lymph node metastasis(P＜0.05).4.The co-expression rate of cyclinB1 and CDC25B in gastric adenocarcinoma was 71.1%(32/45),but there was no significant correlation between the expression of them(P＞0.05).Both of CyclinB1 and CDC25B expression was inversely correlated with P27 expression(P＜0.05).Conclusion1.Expression of CyclinB1 and CDC25B in gastric adenocarcinoma tissues is obviously higher than that in adjacent cancer tissues;expression of CyclinB1 and CDC25B in gastric adenocarcinoma tissues is not associated with the age,sex, clinical stage and lymph node metastasis,but is significantly associated with histological grade.The results suggest that CyclinB1 and CDC25B may participate in the development and progression of gastric adenocarcinoma.2.The positive rate of p27 in gastric adenocarcinoma tissues is significantly lower than that in adjacent cancer tissues;expression of P27 was not associated with histological grade and clinical stage,but was significantly associated with lymph node metastasis.The results suggest that P27 may play a role in the development and metastasis of gastric adenocarcinoma.3.In gastric adenocarcinoma tissues,both of CyclinB1 and CDC25B expression was inversely correlated with P27 expression.The results suggest that these three proteins may play some roles in conjunction with a function in the development and progression of gastric adenocarcinoma.