Clinicopathologic and Biological Significance of Kallikrein 6 Overexpression in Human Gastric Cancer

Purpose: Human kallikrein genes ( KLK ) have been reported to be involved in human malignancies and several KLK s are promising biomarkers of prostate, ovarian, testicular, and breast cancers. Herein, we investigated the clinicopathologic and biological significance of KLK6 gene expression in human gastric cancer. Patients and Methods: Using real-time reverse transcription-PCR, we analyzed the KLK6 expression status with respect to various clinicopathologic variables in 66 patients with gastric cancer. In addition, we established a KLK6 stably suppressed gastric cancer cell line (MKN28) using small interfering RNA–mediated gene silencing, and investigated its effects on the cell proliferation rate, cell cycle, and invasiveness. Results: The KLK6 gene expression in cancerous tissue (0.37 ± 0.53) was significantly ( P < 0.000001) higher than that in noncancerous tissue (0.026 ± 0.060). Elevated KLK6 expression was significantly associated with lymphatic invasion ( P = 0.03). Furthermore, patients with a high KLK6 expression had a significantly poorer survival rate than those with a low KLK6 expression ( P = 0.03). Therefore, we showed that KLK6 gene silencing with KLK6 small interfering RNA effectively suppressed the cell proliferation rate ( P = 0.002), cell population in the S phase ( P < 0.01), and invasiveness ( P < 0.01) in comparison to mock-transfected cells. Conclusions: The KLK6 gene is markedly overexpressed in gastric cancer tissue and its expression status may be a powerful prognostic indicator for patients with gastric cancer. Our findings also suggest that KLK6 may possibly be a novel target for gastric cancer therapy by gene-silencing procedures.