Premium
Disturbed protein–protein interaction networks in metastatic melanoma are associated with worse prognosis and increased functional mutation burden
Author(s) -
Schramm SarahJane,
Li Simone S.,
Jayaswal Vivek,
Fung David C. Y.,
Campain Anna E.,
Pang Chi N. I.,
Scolyer Richard A.,
Yang Yee Hwa,
Mann Graham J.,
Wilkins Marc R.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12126
Subject(s) - melanoma , neuroblastoma ras viral oncogene homolog , mutation , gene , transcriptome , biology , microrna , cancer research , medicine , bioinformatics , oncology , genetics , gene expression , kras
Summary For disseminated melanoma, new prognostic biomarkers and therapeutic targets are urgently needed. The organization of protein–protein interaction networks was assessed via the transcriptomes of four independent studies of metastatic melanoma and related to clinical outcome and MAP ‐kinase pathway mutations ( BRAF / NRAS ). We also examined patient outcome‐related differences in a predicted network of micro RNA s and their targets. The 32 hub genes with the most reproducible survival‐related disturbances in co‐expression with their protein partner genes included oncogenes and tumor suppressors, previously known correlates of prognosis, and other proteins not previously associated with melanoma outcome. Notably, this network‐based gene set could classify patients according to clinical outcomes with 67–80% accuracy among cohorts. Reproducibly disturbed networks were also more likely to have a higher functional mutation burden than would be expected by chance. The disturbed regions of networks are therefore markers of clinically relevant, selectable tumor evolution in melanoma which may carry driver mutations.