Identification and Validation of Kallikrein-Ralated Peptidase 11 As a Novel Prognostic Marker of Gastric Cancer Based on Immunohistochemistry

Background and Objectives: It is important to identify and validate the differentially expressed genes in gastric cancer to screen diagnostic and/or prognostic tumor markers. Methods: cDNA expression microarray, gene set enrichment analysis, and bioinformatics approaches were used to screen the differentially expressed genes between gastric cancer tissues and adjacent non-cancerous mucosa. A novel candidate prognostic marker, Kallikrein-related peptidase 11 (KLK11), was validated in 400 Chinese gastric cancer patients. KLK11 expression in gastric cancer tissues was detected using real-time PCR and Western blot. KLK11 protein expression was further analyzed by immunostaining on tissue microarray, followed with clinicopathological significance and survival analysis. Results: KLK11 expression was significantly decreased in gastric cancer compared with that in normal gastric mucosa (P < 0.001). Furthermore, KLK11 expression was much lower in poorly differentiated cancer samples than that in well-differentiated group (P < 0.01). Survival analysis showed that negative KLK11 expression was associated with nearly fivefold increased risk of distant metastasis after curative gastrectomy (HR 4.65, P < 0.01). Multivariate Cox regression analysis showed that KLK11 expression emerged as a significant independent prognostic factor for disease-free survival and overall survival (P < 0.05). Conclusions: The results indicated that KLK11 expression was decreased in gastric cancer and might serve as a novel independent prognostic marker. J. Surg. Oncol. 2011; 104:516-524. (C) 2011 Wiley-Liss, Inc.