B7-H1Expression Is Associated With Poor Prognosis In Colorectal Carcinoma And Regulates The Proliferation And Invasion Of HCT116Colorectal Cancer Cells

Colorectal carcinoma is the third most frequently diagnosed malignancy in the world andthe fifth leading cause of death among cancer patients in China. Due to a lack of effectivediagnostic markers, most colorectal cancer patients have distant metastases (stage IV) atdiagnosis. The most effective colorectal cancer treatment is surgery. However, the lack ofaccurate prognosis markers makes it difficult to predict patient survival time after surgery.Thus, new and effective markers for diagnosis and prognosis are required in clinic.As the deepening of the molecular mechanism of cancer, especially in colorectal cancer,more and more molecules has been confirmed to participate in the occurrence anddevelopment of CRC. Some molecules has been confirmed to be good early diagnosismarker of colorectal cancer, and could be an independent prognosis predicotor ofcolorectal cancer. However, due to the low specificity and sensitivity, the clinicalapplication of these molecules were not satisfied. Hence, more studies should be conductto confirm the tumor-associatied molecule which could be used as independent prognosispredictor, and it will have important practical significance for the dianosis,prognosis andindividual treatment on the basis of these studies.The co-stimulatory molecule B7homolog1(B7-H1or CD274) is a recently identified ligand for the co-inhibitory receptor programmed death-1(PD-1or CD279). B7-H1isexpressed on T cells, B cells, macrophages and dendritic cells. The expression of B7-H1can be further upregulated upon activation or the presence of IFN-γ. In addition tolymphocytes, B7-H1has also been detected at low levels on cardiac endothelium,microvascular endothelial cells, pancreatic islets and syncytiotropho-blasts in the placenta.Traditionally, the function of B7-H1on antigen-presenting cells is achieved throughbinding with PD-1on T cell, which is thought to have an important role in the inductionand maintenance of immune tolerance.In addition to the expression on lymphocytes and normal tissue, aberrant B7-H1expression has also been found in various human malignancies tumor types includingsquamous cell carcinomas of the lung, esophagus, head and neck, and other types ofcarcinomas such as ovarian, bladder, breast cancer, melanoma and glioma. The expressionof tumor-associated B7-H1is correlated with poor prognosis and high malignancy grade.PD-1expression is upregulated on tumor-infiltrating lymphocytes, and it has beenproposed that B7-H1expressed on cancer cells may inhibit the function of infiltratinglymphocytes. It has also been demonstrated that tumor-associated B7-H1can induceapoptosis of CTL, which subsequently resulted in an escape from T cell-mediated immunesurveillance. Previous study paid excessive attention to the function of tumor-associatedB7-H1which take effect as a ligand for PD-1or CD80, but neglected the effect oftumor-associated B7-H1itself on tumor cell. The study concerning the effect oftumor-associated B7-H1on tumor cell is still in its infancy. Thus, tumor-associated B7-H1may act in concert with other negative regulators of T cell activation to dampen the hostantitumor immune response, also with the great possibility, tumor-associated B7-H1mayaffect the process of cancer progression through interfering the biological function ofcancer cell.In order to evaluate the role of B7-H1played in CRC, we investigated the expression ofB7-H1in143specimens of CRC by immunohistochemistry staining, and analyzed the assciation between the expression of B7-H1and the clinicopathological features of CRCpatients. We aslo analyzed whether B7-H1could be used as an independent prognosispredictor by Cox proportional hazard model. In addition, we knocked down the expressionof B7-H1in HCT116cells by using siRNA, and confirm the effect of B7-H1knockdwonon cell proliferation, cell migration, cell invasion by Flow Cytometry, cell migration andinvasion arrays. Immunohistochemstry results showed the expression of B7-H1washigher in CRC specimens than in adjacent tissues, the postive rate was44.8%and11.4%,respectively. The expression of B7-H1was not detect in normal colon tissues. Stasticalanalysis results showed that the expression of B7-H1in the TNM Ⅲ and Ⅳ patieienswas higher than in TNM Ⅰ and Ⅱ patients. And the expresison of B7-H1wassignificantly correlated with adverse clinicopathological features. Cox proportional hazardshowed B7-H1could be used as an independent prognosis predictor in CRC. Cytologicalexperiments indicated knockdown of B7-H1could promote the apoptosis, and can inhibitthe migration, invasion and the proliferation of HCT116. Base on all these results, we tendto believe B7-H1was involved in the carcinogenesis and development of CRC, andB7-H1was significantly correlated with the adverse clinicopathological features of CRC.More importantly, B7-H1could be used as an independent prognosis predictor of CRC.And B7-H1could directly affect the capacity of cell proliferation, migration, invasion ofHCT116and promote the development of CRC.