AB06. Increased expression of Lgr5 is associated with chemotherapy resistance in human gastric cancer

Objective: To investigate the possibility of Lgr5 being as a specific biomarker in predicting tumor response and overall survival in advanced gastric cancer patients treated with preoperative chemotherapy. The possible association between Lgr5 expression and chemotherapy resistance was also investigated in gastric cancer cell lines.

Methods: Immunohistochemistry for Lgr5 was performed in 68 cases of gastric cancer treated with preoperative chemotherapy. The Lgr5 cDNA was transiently transfected into human gastric cancer cell line BGC-823. The expression of Lgr5 in gastric cancer cell line AGS was inhibited by RNA interference. The expression of mRNA and protein of Lgr5 in cell lines were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blotting. The MTT assay was performed to evaluate cell viability.

Results: Lgr5 expression showed a significant association with the tumor regression grade (TRG) after preoperative chemotherapy. The positive rate of Lgr5 expression in patients with poor tumor regression was significantly higher than in patients with regressed tumor (P=0.001). Lgr5-positive patients had a significantly shorter survival time than Lgr5-negative patients (P=0.001). The overexpression of Lgr5 resulted in a significant resistance to oxaliplatin in BGC-823 cells. Inhibition of Lgr5 expression with small interfering RNA decreased the oxaliplatin resistance in AGS cells.

Conclusions: Lgr5 expression may be implicated in chemoresistance of gastric cancer cells, indicating that Lgr5 is a potential biomarker for predicting chemotherapeutic sensitivity and prognosis in gastric cancer patients and a good potential new therapeutic target for cancer therapy.

Keywords: Lgr5; chemoresistance; gastric cancer; biomarker