Gene network analyses point to the importance of human tissue kallikreins in melanoma progression.
BACKGROUND
A wide variety of high-throughput microarray platforms have been used to identify molecular targets associated with biological and clinical tumor phenotypes by comparing samples representing distinct pathological states.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hospital A,C, Camargo, São Paulo, Brazil. wkerllenmartins@gmail.com
Waleska K
WK
Martins
Gustavo H
GH
Esteves
Otávio M
OM
Almeida
Gisele G
GG
Rezze
Gilles
G
Landman
Sarah M
SM
Marques
Alex F
AF
Carvalho
Luiz F
LF
L Reis
João P
JP
Duprat
Beatriz S
BS
Stolf
D002450:Cell Communication / Q000235:genetics; D018450:Disease Progression; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020840:Tissue Kallikreins / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; C103551:KLK6 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; C495974:Klk7 protein, mouse; D020840:Tissue Kallikreins