Multi-factor COX model analysis of impact of costimulatory molecules B7-H4 on gastric cancer prognosis

Abstract

Objective To study the relation of B7-H4 expression and gastric cancer, and to analyze the impact of different expression levels of costimulatory molecules B7-H4 in gastric cancer tissues on survival time of gastric cancer patients treated with cytokine-induced killer cell biotherapy. Methods 156 gastric cancer patients who received operative treatment and were diagnosed pathologically in the Third Affiliated Hospital, Soochow University, were followed up from Jan. 1, 1998 to Dec. 31,2009. The B7-H4 expression was detected by using immunohistochemical staining and IHS assessment analysis. Demngraphic data, clinical data, recurrence and death time of gastric cancer patients were collected by the method of retrospective cohort study. Impact of B7-H4 high expression on the risk of gastric cancer recurrence and death was analyzed through multi-factor COX model. Results In B7-H4 high expression group and B7-H4 low expression group, the median tumor-free survival time (months) of gastric cancer patients and 95% CI of gastric cancer patients was respectively 16 ( 11.9-20. 1 ) and 47 ( 22.4-71.6 ), and 25 ( 19.0-31.1 )and 43 (35. 2-50. 8). In the chemotherapy group, the median survival time of gastric cancer patients in B7-H4 low expression group was significantly longer than that in B7-H4 high expression group ( 36 vs 16 ,x2 = 14. 14,P 0. 05). In the chemotherapy group, the median tumor-free survival time of gastric cancer patients in B7-H4 low expression group was significantly longer than that in B7-H4 high expression group (33 vs 11, x2= 18. 956,P <0. 01 ). In the chemotherapy plus CIK treatment group, the median tumor-free survival time of gastric cancer patients in B7-H4 low expression group was significantly longer than that in B7-H4 high expression group (90 vs 18 ,x2= 3. 842, P < 0. 05 ). After confounding factors such as sex, age and so on were adjusted, risk of recurrence and death of gastric cancer patients in B7-H4 high expression group was significantly higher than in B7-H4 low expression group ( RR =2. 30, 95% CI = 1.41-3. 75; RR = 1.90, 95% CI =1.20-3.01, respectively). Conclusion B7-H4 high expression may be an independent risk factor of increasing the risk of gastric cancer recurrence and death. CIK cell transfusion treatment can control and interfere in the B7-H4 expression, and prolong the median survival time of gastric cancer patients. B7-H4 low expression of gastric cancer can be considered as inclusion criteria of CIK cell biotherapy. Key words: Stomach carcinoma; B7-H4; Costimulatory molecules; Immunotherapy; Survival time