CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.     

Patients with Helicobacter pylori-positive gastric cancer with human cytomegalovirus infection have a low tendency of advanced lymphatic metastasis in a Chinese population

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV⁻/H. pylori⁻, neither HCMV⁺/H. pylori⁻ nor HCMV⁺/H. pylori⁺ were associated with metastasis, but HCMV⁻/H. pylori⁺ co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.     

Tumor-infiltrating B cell is associated with the control of progression of gastric cancer

This study aimed to further explore the clinicopathological correlation of B cell infiltration in gastric cancer (GC) and its impact on prognostic. By immunohistochemical method, CD20+ B cells, CD3+ T cells, CD66b+ tumor-associated neutrophils, CD163+ tumor-associated macrophages, and CD57+ natural killer cells were analyzed in consecutive sections of 584 GC tissues and 69 normal adjacent tissues. Kaplan–Meier and Cox regression analyses determined the relationship between clinical relevance or prognosis and B cell infiltration. The correlation between total B cell infiltration and various T cell subtype infiltration in GC tissues from 407 patients in the TCGA data was also analyzed. Kaplan–Meier and Cox regression analyses determined the effects of total B cell infiltration and various B cell subtype infiltration on the prognosis of patients with GC. The infiltration level of CD20+ B cells was positively correlated with that of T cells (risk ratio [RR] = 0.0930), especially CD4+ T cells and CD8+ T cells (P < 0.05). A high level of CD20+ B cell infiltration was significantly associated with low lymph node involvement and low TNM stage (P < 0.05). High levels of CD20+ B cell infiltration were significantly associated with improvements in overall survival and disease-free survival. Univariate Cox regression and multivariate Cox regression analysis showed that CD20+ B cell infiltration was an independent protective factor of prognosis. Higher levels of class-switched memory B cell and plasma cell also reflected better overall survival, and class-switched memory B cell and plasma cell were independent protective factors for prognosis. The findings indicate that B cell infiltration in GC, especially switched memory B cells and plasma cells, has a significant effect on tumor progression and prognosis.