Clinicopathological features associated with lymph node metastasis in early gastric cancer: analysis of a single-institution experience in China.

BACKGROUND: An accurate assessment of potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the number of invasive procedures used in cancer therapy is critical for improving the patient's quality of life. OBJECTIVE: To evaluate the clinicopathological features associated with lymph node metastasis of early gastric cancer in patients from a single institution in China. METHODS: A retrospective review of data from 410 patients surgically treated for early gastric cancer at the First Affiliated Hospital (Nanjing, China) between 1998 and 2007, was conducted. The clinicopathological variables associated with lymph node metastasis were evaluated. RESULTS: Lymph node metastasis was observed in 12.20% of patients. The macroscopic type, tumour size, location in the stomach, depth of gastric carcinoma infiltration, and presence of vascular or lymphatic invasion showed a positive correlation with the incidence of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion to be significantly and independently related to lymph node metastasis. The depth of gastric carcinoma infiltration was the strongest predictive factor for lymph node metastasis. For intramucosal cancer, tumour size was the unique risk factor for lymph node metastasis. For submucosal cancer, histological classification and tumour size were independent risk factors for lymph node metastasis. CONCLUSIONS: Histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion are independent risk factors for lymph node metastasis in patients with early gastric cancer in China. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible for highly selected cancers.

c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway.

Aquaporin 3 (AQP3) and c-Met are both overexpressed in human gastric carcinoma and highly associated with its metastasis and invasion. However, it still remains unknown whether c-Met and AQP3 correlate with each other. Herein, we demonstrated that c-Met expression in gastric cancer tissues significantly correlated with differentiation, lymph node metastasis and lymphovascular invasion, and c-Met exhibited marked association with AQP3 expression. Immunoblotting assays showed that hHGF phosphorylated c-Met in SGC7901 and AGS cells and upregulated AQP3 expression in a dose- or time-dependent way. RNAi against c-Met reduced total c-Met levels by about two thirds in both AGS and SGC7901 cells and attenuated hHGF-induced AQP3 expression significantly. In vitro migration and proliferation assays showed that siRNA against AQP3 noticeably restrained HGF-promoted migration and proliferation of these cells. Furthermore, Immunoblotting studies revealed that HGF induced phosphorylation of ERK, and pre-treatment with U0126, a MAPK/ERK inhibitor, partially inhibited hHGF-induced increase in AQP3 expression. Together, these data provide initial evidence that c-Met regulates the expression of AQP3 via the ERK signalling pathway in gastric carcinoma. These findings assist in understanding the mechanism of growth and invasion of gastric carcinoma, and provide a possible strategy for the inhibition of gastric tumor metastasis.

Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance.

BACKGROUND: New evidence for involvement of aquaporins (AQPs) in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. But there is few report concerning the expression and role of AQPs in human gastric carcinogenesis so far. The aim of this current study was to investigate the expression profile of AQPs in human gastric carcinoma and its significance. METHODS: We screened the expression profile of AQP0 approximately AQP12 in gastric adenocarcinoma tissues and corresponding normal mucosa from 89 patients with gastric cancer by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis and immunochemical assay. The relationship between AQPs expression and clinicopathologic characteristics of patients was evaluated. RESULTS: Based on RT-PCR of 13 AQPs examined, AQP1, 3, 4, 5 and 11 were expressed in human gastric cancers or normal gastric tissues, and AQP3, 4 and 5 exhibited differential expression between human gastric carcinomas and corresponding normal tissues, which was confirmed by Western blot analyses. Immunohistochemical assay showed that AQP4 protein was expressed mainly in the membrane of parietal cell and chief cell in the normal gastric mucosa, and absent in carcinoma tissues. AQP3 and AQP5 were detected remarkably stronger in the carcinoma tissues than that in normal mucosa by immunofluorescence. AQP3 expression in cases with undifferentiated tumor was more than that in cases with well-differentiated tumor. Both AQP3 and AQP5 expression were associated with lymph node metastasis and lymphovascular invasion in patients. CONCLUSIONS: These findings of differential expressions of AQPs and their correlation with clinicopathologic characteristics implicated AQPs might play a role in human gastric carcinogenesis.

Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells.

BACKGROUND: Aquaporins (AQPs) are expressed in many different tumor cell types in human. New evidence for the involvement of AQPs in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. AIMS: The aim of this study was to investigate whether AQP3 expression in the human gastric carcinoma cell lines, AGS and SGC7901, enhances cell migration and proliferation. RESULTS: Here, we showed that AQP3 is expressed in the human gastric cancer cell lines, AGS and SGC7901. The hEGF induced AQP3 expression in a time- and dose-dependent manner and increased gastric cancer cell migration and proliferation. AQP3 knockdown by siRNA inhibited hEGF-induced AQP3 expression and thus cell migration and proliferation. Furthermore, a mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 inhibited hEGF-induced AQP3 expression and cell migration or proliferation. METHODS: Cultured AGS or SGC7901 cells were treated with human epidermal growth factor (hEGF) and subjected to cell migration assay and cell proliferation assay. The expression or activation level of proteins was analyzed by western blot. AQP3 knockdown was obtained by small interfering (si)RNA. CONCLUSIONS: Collectively, our findings provide for the first time that AQP3 plays a critical role in hEGF-induced cancer cell migration and proliferation and that hEGF induces AQP3 expression via ERK signal transduction pathways. These finds provide evidence for a novel role of AQP3 in human gastric carcinoma as a potentially important determinant of tumor growth and spread.