The Expression Of B7-H3 And B7-H4 In Hepatocellular Carcinoma And Their Clinical Implications

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The mortality of HCC took the third place among all the malignant tumors and the second place in china. Despite of the development of therapeutic modalities, the overall survival of HCC, however, is still poorer than other malignant tumors. It is partially due to the insensitivity to conventional therapies such as chemotherapy and radiotherapy. But another important reason lies in that the recurrence is still an unfavorable hurdle.It has been well-established that the B7 family encompasses many critical ligands such as B7-1, B7-2, B7-H1, B7-H2 and so on. So far, B7-1, B7-2/CD28 and CTLA-4 pathway as the theory of T lymphocyte co-stimulator or co-inhibitor has been formulated and studied systematically. On that basis, new biomarkers such as B7-H3 and B7-H4 were explored and the important roles they play in the microenvironment of malignant tumor were also recognized in past ten years.B7-H3 and B7-H4 are two members of B7 family discovered in recent years. B7-H3 play important roles in the activation of T lymphocyte and secretion of IFN-γ. However, the role of B7-H3 in tumor microenvironment is still in contrast for clinical observations suggest B7-H3 is exploited by tumors as an immune evasion pathway. B7-H4 is the youngest member of B7 family and the mRNA can be expressed in most kinds of tumor tissues. As early as B7-H4 was discovered, it is counted as playing a co-inhibitory role in the immunity of malignant tumors. It may facilitate the immunologic escape of HCC as it can inhibit the proliferation of T lymphocyte and secretion of corresponding cytokines.PartⅠThe Expression of B7-H3 in Hepatocellular Carcinoma and its Clinical Implications in Metastasis and RecurrenceThe aim of this study is to evaluate the expression pattern and the predictive value of B7-H3 in the prognosis of patients and the recurrence of HCC as well as discuss the clinical implications.A total of 2,523 eligible cases were identified from the database composed of patients underwent curative liver resection between January 2002 and September 2006. The inclusion and exclusion criteria were as following:(a) distinctive pathologic diagnosis, (b) without preoperative anticancer treatment and distant metastases, (c) curative liver resection, (d) with a complete clinicopathologic and follow-up data.240 patients were selected from this cohort at random. The corresponding blocks were manufactured into two groups of tissue microarray:group HCC and their corresponding tumor adjacent tissues respectively.The expression of B7-H3 in HCC were studied by immunohistochemistry. Statistical analyses were done by SPSS 16.0 statistical software (SPSS). Chi-square test was used to analyze the difference among groups. Univariate analysis was calculated by the Kaplan-Meier method (the log-rank test). Multivariate analysis was done using the Cox multivariate proportional hazards regression model with stepwise manner (forward, likelihood ratio). Mann-Whitney rank sum test was used for comparison of survival times between groups.Nine human HCC cell lines were used, including L0-2,SMMC7721,PLC,HepG2, Hep3B,MHCC97L,MHCC97H,HCCLM3,HCCLM6. The latter four lines are from the same parental cell line--MHCC97, with stepwise metastatic potential (MHCC97L