A gene expression signature associated with survival in metastatic melanoma.
BACKGROUND
Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival.


METHODS
Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction.


RESULTS
SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival.


CONCLUSIONS
The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.
Mandruzzato
Susanna
S
Oncology Section, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy. susanna.mandruzzato@unipd.it
Callegaro
Andrea
A
Turcatel
Gianluca
G
Francescato
Samuela
S
Montesco
Maria C
MC
Chiarion-Sileni
Vanna
V
Mocellin
Simone
S
Rossi
Carlo R
CR
Bicciato
Silvio
S
Wang
Ena
E
Marincola
Francesco M
FM
Zanovello
Paola
P