The Expression Of Co-stimulatory Molecule B7-H2 In The Peripheral Blood Of Colorectal Cancer Patients And Its Clinical Significance

Colorectal cancer(CRC) is the third most frequently diagnosed malignancy at home and abroad and the fifth leading cause of death among cancer patients in China. Due to a lack of effective diagnostic markers, most colorectal cancer patients have been middle and terminal cancer(stageⅢ,Ⅳ),even to the extend that they have distant metastases(stageⅣ) at diagnosis. The most effective colorectal cancer treatment is surgery. However, the lack of accurate 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 research of the molecular mechanism of tumor, especially in colorectal cancer, more and more molecules has been confirmed to participate in the occurrence and development of CRC. Some molecules has been confirmed to be good and early diagnosis marker of colorectal cancer, and could be an independent prognosis predictor of colorectal cancer. However, due to the low sensitivity and specificity, the clinical application of these molecules were not satisfied. Hence, more studies should be conducted to confirm the tumor-associated molecule which could be used as independent prognosis predictor, and it will have important and clinical significance for the diagnosis, individual treatment and prognosis on the basis of these studies.The co-stimulatory molecule B7 homolog 2(B7-H2,CD275,B7RP-1,GL50,ICOSL) is a new member of B7 family and reported in October,2000 first.B7-H2 is a positive co-stimulatory molecule and first found in the mouse by Yoshinaga et al. B7-H2 can promote T cell proliferation, cytokine secretion and prevent cells apoptosis. It has been recently identified that it is a ligand for the inducible co-stimulatory receptor on activated memory T cells, ICOS. When B7-H2 interacted with its receptor, ICOS, it can stimulate T cell-mediated immune response.Basic characteristics and immune regulatory mechanisms of co-stimulatory molecules play an important role in clinical diagnosis and therapy. Now, there are some reports about B7-H2 expression in tumor cells and B7-H2 gene study in tumor patients, but hardly about B7-H2 expression in the peripheral blood of cancer patients. However, the precise role of B7-H2 in tumor immunity is still ambiguous, so the aim of our present work is to investigate the expression of B7-H2, carcino-embryonic antigen(CEA)、carbohydrate antigen(CA)125 and CA19-9 by flow cytometry and electrochemical luminescence in the peripheral blood of colorectal cancer and to analyze the associations between B7-H2 expression on peripheral B cells and clinicopathological parameters and whether B7-H2 could be an independent predictor in our independent cohort research of CRC patients.AIM: To investigate the expression of B7-H2 on the CD19+B cells in the peripheral blood of CRC patients and to detect the levels of CEA, CA125 and CA19-9 in the peripheral blood. And then to investigate the correlation between B7-H2,CEA,CA125,CA19-9 and clinical parameters. Furthermore, to investigate the potential role of B7-H2 in diagnosis and prognosis estimation of colorectal cancer.METHODS: The objects were the peripheral blood of 80 primary colorectal cancer and 50 healthy controls. Flow cytometry method was used to detect the expression of B7-H2 on CD19+B cells in the peripheral blood. And electrochemical luminescence was used to detect the expression of CEA,CA125 and CA19-9 in the serum. the association between the expression of B7-H2, CEA, CA125,CA19-9 and clinicopathological parameters were analyzed by statistical methods. Quantitative data were processed with statistical software SPSS 19.0.The statistical significance between the expression of B7-H2,CEA,CA125,CA19-9 and clinicopathological parameters in the control group and the case group was assessed by Mann-Whitney U test or One-way analysis of variance. Survival analysis about whether B7-H2 being used as an independent prognosis predictor was performed according to COX proportional hazard model. The level of statistical significance was established at P<0.05. Charts and graph were drawn with Graph Pad Prism 5.0.RESULTS:(1) Results showed that compared with the healthy control group, the expression of B7-H2 on CD19+B cells in the peripheral blood of CRC patients was significantly lower in the CRC patients(P < 0.01).(2) The expression of B7-H2 on CD19+B cells in the peripheral blood was correlated with the patients, Dukes stage, differentiation degree, lymph node metastasis, distant metastasis and survival time(P < 0.05).(3) The expression of B7-H2 on CD19+B cells in the peripheral blood was not correlated with the patients,gender, age, tumor position and mucoid carcinoma(P > 0.05).(4)The expression level of CEA, CA125 and CA199 in the serum was related with tumor stage, lymph node metastasis and distant metastasis(P < 0.05).(5) The expression level of CEA, CA125 and CA199 in the serum was not related with gender, age, tumor position, differentiation degree and mucoid carcinoma(P > 0.05).(6)The expression of B7-H2 in the peripheral blood could be used as an independent prognosis predictor in CRC.CONCLUSION: The expression of B7-H2 was abnormally decreased in the peripheral blood of CRC. The abnormally expression of B7-H2 was different in different tumor stage, differentiation degree and lymph node metastasis. Suggesting that B7-H2 may participate in the development of CRC by promoting the abnormal activation of T and B cells. It will have potential value in clinical medicine.B7-H2 could be used as an independent prognosis predictor. B7-H2 detection with CEA, CA125 and CA19-9 might improve the accuracy of CRC diagnosis and prognosis estimation. The expression of B7-H2 in the peripheral blood could be used as an independent prognosis predictor in CRC.