Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma

Oncotarget
Ricardo D LardoneDelphine J Lee

Abstract

Platform and study differences in prognostic signatures from metastatic melanoma (MM) gene expression reports often hinder consensus arrival. We performed survival/outcome-based pairwise comparisons of three independent MM gene expression profiles using the threshold-free algorithm rank-rank hypergeometric overlap analysis (RRHO). We found statistically significant overlap for genes overexpressed in favorable outcome (FO) groups, but no overlap for poor outcome (PO) groups. This "favorable outcome signature" (FOS) of 228 genes coinciding on all three overlapping gene lists showed immune function predominated in FO MM. Surprisingly, specific cell signature-enrichment analysis showed B cell-associated genes enriched in FO MM, along with T cell-associated genes. Higher levels of B and T cells (p<0.05) and their relative proximity (p<0.05) were detected in FO-to-PO tumor comparisons from an independent MM patients cohort. Finally, expression of FOS in two independent Stage III MM tumor datasets correctly predicted clinical outcome in 12/14 and 44/70 patients using a weighted gene voting classifier (area under the curve values 0.96 and 0.75, respectively). This RRHO-based, cross-study analysis emphasizes the RRHO approach power, con...Continue Reading

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Mar 11, 2017·Targeted Oncology·Nicole J FlynnJennifer Sims-Mourtada
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Methods Mentioned

BETA
biopsies
Profiler
exome sequencing

Software Mentioned

GEP
ImageJ2
Gene Enrichment Profiler
Ingenuity Pathway Analysis ( IPA )
GraphPad
REduce and
RRHO
STRING
Ingenuity Pathway Analysis
Fiji ImageJ

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