Abstract
BackgroundCurrent 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.MethodsForty-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.ResultsSAM 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.ConclusionThe 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.
Highlights
Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome
Two stage IV patients with subcutaneous and lung metastases respectively were affected by ocular melanoma
This study applied high-throughput gene microarrays to screen the transcriptome in the search for genes correlated with patient survival
Summary
Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. Patients in the same TNM stage can have very different clinical outcomes, which is true for TNM stage III. The most useful prognostic factors in metastatic disease are the metastatic site (e.g. subcutaneous vs visceral localization) and lactate dehyrogenase (LDH) plasma levels [2,3,4]. Despite significant efforts to identify independent predictors of melanoma outcome, no generally accepted histopathological or molecular marker defines disease subsets with clinically different outcomes [5,6,7]. Understanding differences in clinical behavior is important in the design and analysis of clinical trials, and in planning different therapeutic strategies, such as adjuvant treatment
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