Gene network analyses point to the importance of human tissue kallikreins in melanoma progression

The gene expression profiles of human cutaneous melanomas were determined by cDNA microarray analysis. Next, a robust analysis to determine functional classifications and make predictions based on data-oriented hypotheses was performed. Relevant networks that may be implicated in melanoma progression were also considered.In this study we aimed to analyze coordinated gene expression changes to find molecular pathways involved in melanoma progression. To achieve this goal, ontologically-linked modules with coordinated expression changes in melanoma samples were identified. With this approach, we detected several gene networks related to different modules that were induced or repressed during melanoma progression. Among them we observed high coordinated expression levels of genes involved in a) cell communication (KRT4, VWF and COMP); b) epidermal development (KLK7, LAMA3 and EVPL); and c) functionally related to kallikreins (EVPL, KLK6, KLK7, KLK8, SERPINB13, SERPING1 and SLPI). Our data also indicated that hKLK7 protein expression was significantly associated with good prognosis and survival.Our findings, derived from a different type of analysis of microarray data, highlight the importance of analyzing coordinated gene expression to find molecular pathways involved in melanoma progression.Cutaneous melanoma is considered a complex multigenic and multifactorial disease that involves both environmental and genetic factors [1-3]. Its tumorigenesis is often explained as a progressive transformation of normal melanocytes to nevi that subsequently develop into primary cutaneous melanomas (PCM) [4,5]. In fact, the development of PCM is a classical example of a neoplasm progression through discrete stages with well-known clinical and histological features. In spite of its obvious oversimplification, this model incorporates the notion that signals triggered by cell-cell and cell-extracellular matrix interactions are critical for maintaining melanocyte homeostasis [6]. Deregu