CD155 Expression And Its Clinical Value In Human Cholangiocarcinoma

Background and purpose Cholangiocarcinoma originates in the bile duct epithelium and is one of the most malignant tumors.Early invasion and metastasis is the most important biological characteristic.At present,radical surgery is still the primary treatment for cholangiocarcinoma.However,due to its unconspicuous symptoms and lack of effective diagnosis at the early stage,most patients have entered the advanced stage when they are first diagnosed with cholangiocarcinoma.Owing to severe local invasion and distant metastases,many patients had missed the optimal timing for radical surgery,which is one of the important reasons leading to low survival rate.CD155(PVR,poliovirus receptor)is a highly glycosylated type I transmembrane protein and belongs to the immunoglobulin superfamily(Ig SF).As an important tumor-associated protein,CD155 overexpression and its impact on tumor cells have been confirmed in different kinds of human tumors by previous studies.However,there have been no report about CD155 in cholangiocarcinoma.Based on the above research background,we use immunohistochemistry,Western blot and q RT-PCR method to detect the expression of CD155 in human cholangiocarcinoma tissues and adjacent normal bile duct tissues.This study evaluated the correlation between CD155 expression and tumor angiogenesis,clinicopathological parameters.And we also analyzed the prognostic value of CD155.Method(1)CD155 expression was investigated in 20 paired CCA tissues and corresponding paracancerous tissues by Western blotting and real-time polymerase chain reaction assays at protein and m RNA levels.The difference between them was also analyzed.(2)CD155 expression in 90 paired cholangiocarcinoma tissues and adjacent normal tissues was detected by immunohistochemistry.The difference between them was also analyzed.(3)The expression of VEGF and CD31(labeled vascular endothelial cells)in 90 cholangiocarcinoma tissues were detected by immunohistochemistry.The correlation between CD155 with VEGF and microvessel density(MVD,microvessel density)in cholangiocarcinoma tissues was also analyzed.(4)According to the immunohistochemistry results and patients' clinicopathological data,the relationship between CD155 expression and clinicopathological parameters was analyzed by chi-square test.(5)The relationship between the level of CD155 expression and patient survival time was analyzed with Kaplan–Meier survival analysis and the log-rank test.Multivariate survival analysis was implemented by Cox proportional hazards regression model to ascertain the independent prognostic.Results(1)The Western blot and q RT-PCR results showed CD155 expression was significantly upregulated in tumor sample tissues than that in adjacent nontumor tissues(P <0.05).(2)The immunohistochemistry results showed that CD155 expression was remarkably higher in CCA tumor tissue samples when compared to adjacent nontumorous tissue samples(P <0.001).(3)CD155 expression was positively correlated with VEGF(r = 0.481,P <0.001)and MVD(r = 0.442,P <0.001)in cholangiocarcinoma tissues.(4)CD155 expression level was significantly related to histological grade(P=0.002),LNM(P<0.001),and TNM(P=0.03).However,it had no significant association with other parameters such as age,gender,tumor size,tumor location,PNI,serum CA19–9,and serum CEA.(5)The Kaplan-Meier survival curves showed that the high expression level of CD155 was associated with shorter overall survival(OS)(P <0.001)and disease-free survival(DFS).Multivariate survival analysis revealed that CD155 expression served as an independent prognostic factor for DFS(HR = 3.353,95% CI 1.752-6.416,P <0.001)and OS(HR = 3.995,95% CI 1.985-8.093,P <0.001).Conclusion Our study showed that CD155 expression was significantly upregulated in tumor sample tissues than that in adjacent nontumor tissues.More importantly,CD155 expression level in tumor tissue was closely related to tumor differentiation,tumor stage,lymph node metastasis and angiogenesis in cholangiocarcinoma.The upregulated CD155 expression level was associated with poor prognosis in cholangiocarcinoma and served as an independent predictor of unfavorable prognosis in patients after surgery.Our results revealed that upregulated CD155 played an important role in tumor occurrence and development process and it may be a promising prognostic biomarker for the cholangiocarcinoma patients.