059 Différentiel expression of the kallikrein 5 and kallikrein 7 gènes in non-small cell lung cancers subtypes

Abstract

Human tissue kallikreins (hKs) are secreted serine protéases with diverse expression patterns and physiological rôles. Several members of the kallikrein gène (KLK) family, which now includes 15 gènes, are differentially expressed in various cancers and some émerge as useful diagnostic/ prognostic markers for hormone dépendent cancers. Although clinically effective non-invasive meth-ods for early détection and screening of lung cancer are lacking, analysis of kallikrein gène expression has never been performed in lung. The aim of this study was to investigate KLK5 and KLK7 gene expression in non small-cell lung cancers (NSCLC). We used both RT-PCR and Western blotting to analyse KLK5 and KLK7 gène expression and their respective products (hK5 and hK7) in lung. Gène expression was then quantified by real-time PCR in matched malignant and nonmalignant lung tissue samples obtained from 56 patients with NSCLC and results were compared to clinico-pathological parameters. We detected for the first time the expression of both KLK5 and KLK7 gènes and their protein products (hK5 and hK7) in tumoral and nontumoral lung tissues. A significant increase in KLK5 expression was observed in squamous cell carcinoma (P = 0.02) compared to matched nontumoral tissue, whereas KLK7 expression was decreased in adenocarcinoma (P = 0.003). In non-cancerous tissues, multivariate analysis revealed a négative corrélation between KLK5 expression and the metastatic status of the paired tumors (P = 0.05) and, a positive corrélation between KLK7 expression and tumor differentiation (P = 0.02). In cancerous tissues, KLK5 and KLK7 expressions were mainly associated with squamous cell carcinoma (P = 0.04 and P = 0.01, respectively). Fur-thermore, KLK7 expression correlated positively with differentiation (P = 0.03) and negatively with adenocarcinoma histotype (P = 0.003). Our results demonstrate that KLK5 and KLK7 are differentially expressed in NSCLC subtypes and indicate that the variability in KLK5 and KLK7 expressions hâve to be taken into account not only to better understand the lung tumorogenesis but also for clinical purposes.