Relation between Caspase recruitment domain-containing membrane-associated guanylate kinase protein 1, clinicopathological features of gastrointestinal lymphoma also and Helicobacter pylori infection

Abstract

Objective To investigate the relation between the expression of Caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1),clinicopathological features of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma,diffuse large B cell lymphoma (DLBCL),and Helicobacter pylori (H.pylori) infection.Methods From January 1999 to March 2011,34 patients with DLBCL and 20 patients with MALT lymphoma were selected,and at same period 21 cases with reactive hyperplasia of gastrointestinal lymphoid tissue were enrolled in as control.The expression of CARMA1,Ki-67 and cytotoxin-associated gene A (CagA) at protein level were examined by immunohistochemistry.The relative expression quantity of CARMA1 mRNA was detected by real-time polymerase chain reaction (PCR).The condition of H.pylori infection in 25 gastric lymphoma and 10 controls was detected by methylene boric acid and blue staining or semi-nested PCR.Chi-square test was used for counting data analysis,t test for measurement data.Multivariate COX regression analysis was implemented for survival analysis.Survival curve was drawn by Kaplan-Meier method and analyzed by Log-rank test.Results The relative expression quantity of CARMA1 mRNA of 28 patients with DLBLC (3.073±1.846) was higher than that of 14 patients with MALT lymphoma,and the difference was statistically significant (F 0.975,P＜ 0.05).The positive rate of CARMA1 expression at protein level of gastrointestinal lymphoma group (75.9 ％,41/54) was higher than that of control group (47.6％,10/21),and the difference was statistically significant (x2 =5.568,P＜0.05),and the positive rate of CARMA1 expression of MALT lymphoma group (11/20) was lower than that of DLBCL group (88.2％,30/34),and the difference was statistically significant (x2 =5.900,P＜0.05).Among 42 patients with gastrointestinal lymphoma who received surgery,the relative expression quantity of CARMA1 mRNA in cases with high proliferation (2.885±1.837) was higher than that in cases with low proliferation.The expression of CARMA1 mRNA in the cases at advanced stage of the disease (4.416± 1.010) was higher than that in cases at early stage,and the difference was statistically significant (F=3.317 and 2.972,both P＜0.05).Among 54 patients with gastrointestinal lymphoma,the positive rate of CARMA1 expression at protein level of patients with high proliferation (88.6％,31/35) was higher that that of patients with low proliferation (10/19),and the difference was statistically significant (x22 ＝ 6.847,P＜0.05).There were no significant differences in relative expression quantity of CARMA1 mRNA and the positive rate of CARMA1 expression at protein level between 11 gastric lymphoma patients without H.pylori infection and 14 gastric lymphoma patients with H.pylori infection (both P＞0.05).The positive rate of CARMA1 expression at protein level of CagA positive and CagA negative H.pylori infected gastric lymphoma patients was 11/11 and 2/3.The expression of CARMA1 at protein level was correlated with the prognosis of gastrointestinal lymphoma (RR＝4.160,P＜0.05).In the 29 cases of patients with gastrointestinal MALT lymphoma and 18 cases of patients with DLBCL who were followed up,the survival situation of gastrointestinal lymphoma patients with CARMA1 positive expression rate over 50％ was worse than that of patients with the rate less than 50％,and the difference was statistically significant (x2=5.383 and 4.028,both P＜0.05).Conclusions CARMA1 might be involved in the pathogenesis and progression of MALT and DLBCL; and it might be a related factor of poor prognosis.There was no correlation between the expression of CARMA1 and H.pylori infection in these two lymphomas. Key words: Lymphoma; CARMA1; Helicobacter pylori