AB05. Lgr5 is associated with invasion, metastasis and poor prognosis in human gastric carcinoma

Objective: To explore Lgr5 expression in gastric carcinoma and analyze its role in invasion, metastasis and prognosis in carcinoma.

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess Lgr5 mRNA and MMP2 mRNA in a normal gastric mucosa cell line and carcinoma cell lines. Immunohistochemistry for Lgr5 and MMP2 was performed in 318 cases of gastric carcinoma. Western blotting was used to analyze Lgr5 expression in the cell lines and to determine the expression of Lgr5 and MMP2 in 75 cases of gastric carcinoma and matched normal mucosa.

Results: Lgr5 mRNA and protein expression was significantly higher in gastric carcinoma than that in normal mucosa (all P=0.001). Lgr5 expression was more frequent in advanced T-stage cancer and was found to correlated with metastasis in the regional lymph nodes (P=0.001) and distant (P=0.013). Multivariate analysis showed that Lgr5 had an independent effect on survival (P=0.001). Lgr5 was positively correlated with MMP2 (P=0.001, r=0.485). According to Western blot analysis, correlation was observed between Lgr5 and MMP2 expression in carcinoma (P=0.001, r=0.875). The mean relative expression level of Lgr5 protein was significantly elevated in advanced degree of tumor infiltration (P=0.001). Expression of Lgr5 protein was increased in tumor with metastasis (whatever lymph node metastasis or distant metastasis) compared with nonmetastatic cancer tissue (P=0.001).

Conclusions: Lgr5 may play important roles in the in invasion, metastasis and prognosis of gastric carcinoma, and thus may become a useful target for therapeutic intervention and a potential indicator for clinical assessment of tumor prognosis.

Keywords: Lgr5; gastric carcinoma; tumor prognosis; MMP2