Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma

AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery,and none of them received preoperative radiochemotherapy.Normal proximal adjacent bowel tissue,which served as an internal control,was obtained from 52 randomly selected patients.Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesisrelated protein HIF-1αin normal colorectal tissues and colorectal carcinoma tissues.The relationships between the expression and clinical characters and prognosis were analyzed.RESULTS:HIF-1αand Sema4D were positively expressed in 58%and 60%of colorectal carcinoma tissues,respectively.Significantly lower expression levels were observed in normal mucosa(8%and 12%,respectively).HIF-1αand Sema4D expression was closely correlated with histological tumor type,tumornode-metastasis(TNM)stage,and lymphatic metastasis(P<0.05),but not with age or tumor size(P>0.05).HIF-1αand Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma,as determined by Spearman rank correlation analysis(r=0.567;P<0.01).Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis(P<0.05).CONCLUSION:These findings suggest that HIF-1αand Sema4D expression correlates with histological tumor type,TNM stage,and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Promotion of Sema4D expression by tumor-associated macrophages: Significance in gastric carcinoma

AIM To study the role of semaphorin 4 D(Sema4 D) expression promoted by tumor-associated macrophages(TAMs) in gastric carcinoma cells and its clinical significance in the invasion and metastasis of gastric carcinoma.METHODS CD68 and Sema4 D expression was analyzed in gastric carcinoma and adjacent normal tissues from 290 patients using the immunohistochemical streptavidinperoxidase method, and their relationships with clinicopathological features were evaluated. Human M2 macrophages were induced in vitro and co-cultured in non-contact with gastric carcinoma SGC-7901 cells. Changes in the secretory Sema4 D level in the SGC-7901 cell supernatant were measured using an enzymelinked immunosorbent assay. The effects of TAMs on SGC-7901 cell invasion and migration were assessed with invasion and migration assays, respectively.RESULTS CD68 and Sema4 D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues(71.7% vs 33.8% and 74.5% vs 42.8%, respectively; P < 0.01). CD68 and Sema4 D protein expression was significantly associated with histological differentiation, TNM stage, and lymph node metastasis(P < 0.05), and their expression levels were positively correlated with one another(r = 0.467, P < 0.01). In the in vitro experiment, secretory Sema4 D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control(1224.13 ± 29.43 vs 637.15 ± 33.84, P < 0.01). Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays(P < 0.01).CONCLUSION TAMs promote the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4 D protein expression. Combined detection of TAM markers, CD68 and Sema4 D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.