| Objective To investigate the expression and biological significance of CD40 in gastric cancer. To explore the correlation of CD138, gelsolin, P53 and NF- k B with CD40 in gastric cancer. The relationship between CD40 and apoptosis was analyzed. To measure the level of soluble CD40 ligand (sCD40L) in the patients with gastric cancer and identify its biological significance.Methods Expressions of CD40 with associate molecules CD138, gelsolin, P53 and P65 were evaluated by immunohistochemistry in human gastric cancer tissues (56 cases) and adjacent nomal gastric tissues (32 cases). Apoptosis of gastric cancer cell was detected by TUNEL to determine apoptotic index (AI). The serum levels of soluble CD40 ligand were measured with enzyme linked immunosorbent assay in 15 healthy contrals, 10 patients with gastric ulcer and 45 patients with gastric cancer. The changes of sCD40L from preoperative to postoperative were analyzed in 10 patients with gastric cancer.Result 1. The immunoreactivity of CD40 increased in 19/56 gastric cancer tissues (33.9%) as compared to the tumor-free tissues (4.5%),respectively (p<0.01). Expressions of CD138 and gelsolin were detected in a significantly less proportion of gastric cancer samples (44.6%, 10.7%) than adjacent normal gastric tissues (96.9%, 81.3%)(p<0.01-0.05). The positive rates of P53 and P65 expression in gastric cancer tissues (69.6%, 64.3%) were significantly elevated compared with the tumor-free tissues (p<0.01). 2. CD40 expression showed no significant relationship with tumor size , histological types and invasion deep (p>0.05), while was closely correlated with lymph node metastasis, metastatic spread and TNM stage (p<0.01-0.05). The loss of CD138 and gelsolin expression was significantly correlated with lymph node metastasis (p<0.01), but not with tumor size. P53 expression showed significant relationship with tumor size and histological types (p<0.05). There was positively relationship between P65 expression in gastric cancer tissue and tumor size , histological types, lymph node metastasis and invasion deep (p<0.01-0.05). 3. The expression of CD40 was inversely correlated with CD138 (r=0.375, p<0.05) while positively with P53 and P65 (r=0.201,0.277; p<0.01). 4. AI of gastric cancer tissues was 1.16 + 0.37. The expression of CD40 was inversely correlated with AI. 5. Serum concentration of soluble CD40 ligand was significantly elevated in the patients with gastric cancer (3.57+1,63ng/ml) in comparision with healthy control subjects(l .94 + 0.86ng/ml) (p<0.01), and the levels of postoperative (n=10) sCD40L was significantly lower than preoperative's (p<0.05). The level of sCD40Lexpression were closely correlated with invasion deep, with lymph node metastasis, with TNM stage.Conclusions 1. CD40 expression was upregulated in gastric cancer tissues as compared to the tumor-free tissues and was closely correlated with lymph node metastasis, metastatic spread and TNM stage. It indicated measurement of CD40 expression in gastric cancer helps a lot in diagnosis and evaluation of prognosis of gastric cancer and CD40 might be a useful therapeutic target for biological therapy of gastric cancer. 2. The expression of CD40 was inversely correlated with CD138 while positively with P53 and P65 in gastric cancer tissues. It showed CD40 might provide some effects on the pathogenesis of gastric cancer by regulate the expressions of tumor suppressor genes, cell adhesion moleculars and signaling transduct factors. 3. The expression of CD40 was inversely correlated with AI. It might play an vital role during human gastric carcinogenesis through inhibiting the apoptosis of gastric cancer cells. 4. There was significant relationship between the serum concentration of soluble CD40 ligand and biological behaviors of gastric cancer. Examination of sCD40L in the serum of patients with gastric cancer helps a lot in evaluating invasion deep, intensity of lymph node metastasis, TNM stage and prognosis.
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