Expression And Clinical Significance Of Cip2a And Opn In Bladder Cancer

Bladder cancer is a common clinical cancer. In the worldwide, it ranked fourth in the male common cancer and ninth in the died caused by cancer. The male to female ratio of death caused by cancer was about3:1. According to statistics, in2010it was approximately70,530cases of new cancer patients and14,680cases of cancer-related deaths in the United States. Although many cases of bladder cancer occurs when there is no obvious exposure to oncogenes, but oncogene has many predisposing factors. The incidence of bladder cancer has related with the geography, environment, race, sex, schistosome infection, smoking, occupational exposure and genetic susceptibility and other factors. Direct or indirect effects of external factors, can induce DNA abnormalities of urothelial cell, which led to the final common biological pathway of uncontrolled cell growth of bladder cancer. The development of bladder cancer is a multi-step process. It has different molecular genetic alterations in tumor development at each stage, the abnormal changes in long-term accumulation of these genotypes eventually led to the emergence of the malignant phenotype. Molecular genetic alterations of bladder cancer mainly include two categories:one change is bound up with the low grade of tumor. Such changes are promoting cell proliferation, but have little or no effect on the role of the cellular micro environment, cell differentiation,cell death and apoptosis. Another change occurred with the high-grade tumors. Such changes lead to uncontrolled cell proliferation, loss regulation of cell cycle and apoptosis and is closely related to cell differentiation. In the process of normal epithelial cells develop to tumor cells, it involves changes of many genes, including oncogenes, tumor suppressor genes, cell cycle-related genes, apoptosis related genes,and DNA damage repair related genes.In oncology frontier, As a key regulator of the cancerous inhibitor of protein phosphatase2A(CIP2A),it closely related with the occurrence and development of many cancers, thus causing great interest. As a newly discovered proto-oncogene, CIP2A acted by stabilizing the C-Myc, promoting cell proliferation and anchor independent growth,and redardanting aging and differentiation to promote the occurrence and development of malignant tumors in vivo. Thus causing great concern. This paper has a preliminary study to research whether CIP2A could be a diagnostic marker of bladder cancer. At the molecular level, we screened46cases of fresh bladder epithelial tissue specimens, including38cases of bladder urothelial carcinoma,8cases of normal bladder transitional epithelium, we have verified29cases (76.32%) detection of CIP2A mRNA expression of tumor tissue samples in38cases,it was not detected CIP2A mRNA in8cases of normal bladder transitional epithelium. At the protein level, we screened111cases of paraffin tissue samples, including99cases of bladder urothelial cancer tissue,12cases of normal bladder epithelium, to make slices,we use immunohistochemical staining to detect the protein expression of CIP2A in bladder urothelial carcinoma. It does not found CIP2A protein expression in normal tissues. However it expressed the protein of CIP2A in63cases (63.64%) of99cases of bladder urothelial carcinoma. This shows that CIP2A has more specific expression in bladder cancer. Therefore CIP2A may be applied as a new tumor marker in the diagnosis of bladder tumors. At the same time it needs further in-depth study to confirm that it can be act as a therapeutic targets.Osteopontin (osteopontin, OPN) is a secreted phosphorylated glycoprotein with multiple functions, which promoted cell adhesion and migration, considered to be a malignant transformation of secretory protein and widely distributed. Its expression levels in tumor tissue and blood of patients with malignant cancer has an important contact of patients screened, disease prediction and prognosis. In recent years, a growing number of studies have found that OPN plays a role by means of binding the cell membrane receptor CD44and integrin, it is closely related with tumor cell growth, proliferation, invasion and metastasis. It is highly expressed in breast, liver and the majority of tumors. In the Yeatman’s molecules Encyclopedia of new tumor markers and tumor progression markers, OPN has been identified as a clinical marker of choice. The topic selected90bladder tissue paraffin-embedded specimens of clinical sources(including80cases of bladder urothelial carcinoma and10cases of normal) to make slices to analyze OPN protein expression in bladder urothelial carcinoma and normal transitional epithelium by using immunohistochemical techniques at the protein level. CIP2A protein expression was negative in most normal tissue case (80.00%). However59cases (73.75%) were positive expression in80cases of bladder urothelial carcinoma. This shows that compared to normal bladder epithelial tissue, OPN has a certain degree of specificity, it is possible to become a molecular marker of early screening and diagnosis of bladder urothelial c arcinoma.Finally, the statistical analysis of immunohistochemical results can be seen that the expression of CIP2A has no clear correlation of the patient’s age, gender, clinical stage, grade, and organization pathological type of such clinical indicators. But CIP2A and OPN protein expression have a significant correlation in tissue samples of bladder urothelial carcinoma, suggesting that it has statistical significance of the coordinated expression of the protein. And both CIP2A, OPN protein expressed in the cytoplasm, and some nuclei were also positive expression, also shows the consistency of both the location and the intensity of expression. The coordinated expression of results of CIP2A and OPN at the protein level of clinical specimens by immunohistochemistry, suggesting that the combination use as the bladder tumor markers has prospects of both research and application.In summary, we started from the clinical practice, using clinical tissue samples and clinical data, to reveal the mechanism of the coordinated expression and the value of possible clinical application of CIP2A and osteopontin, tumor or interstitial derived, in the perspective of genetic and biochemical regulation. The function of the effectiveness of CIP2A and osteopontin protein in tumorigenesis in the previous studies and the highlight significance in this subject of clinical specimens, show the possibility that CIP2A and OPN can be the diagnostic molecular markers of bladder urothelial carcinoma. Further understanding the relevant regulation of signal transduction pathways of CIP2A and osteopontin, will be helpful to the possibility of these two molecular markers worked as new molecular diagnostics and targeted therapy markers against cancer.