Fig. 2: De novo pan-cancer molecular subtypes as defined by mass-spectrometry-based proteomics.
a By ConsensusClusterPlus32 of 532 proteomic profiles in the CPTAC Confirmation/Discovery cohort, 10 proteomic-based subtypes—k1 through k10—were identified (columns). For these same cases, pan-cancer class assignments—c1 through c10—based on the previous pan32 mRNA-based discovery2 were also made (rows, mapping the previous pan32 mRNA classifier to CPTAC protein expression patterns). Significances of overlap between the two sets of classifications are represented. P-values by one-sided Fisher’s exact test. b For CPTAC Confirmation/Discovery cohort, differential expression patterns (values normalized within each tissue-based cancer type; SD, standard deviation from the median) for a set of 1000 proteins (top heat map) and for a set of 500 phospho-proteins (bottom heat map) found to best distinguish between the 10 proteome-based subtypes (see the “Methods” section, top 100 over-expressed proteins for each subtype). Proteins highlighted by name have GO annotation “cell surface receptor signaling pathway” and DrugBank association (lists provide examples of differentially expressed proteins but these would not necessarily have more importance over the other proteins in the heat map, full lists provided in Supplementary Datas 2 and 3). c For the TCGA pan32 cohort (n = 10,224 cases), we made CPTAC-based pan-cancer subtype assignments (columns, mapping the CPTAC protein expression patterns to TCGA mRNA patterns). Significances of overlap between the CPTAC-based subtypes (columns, k1 through k10) to the previous pan32 mRNA-based pan-cancer class assignments2 (rows, c1 through c10) are represented. P-values by one-sided Fisher’s exact test. d For each cancer type represented in CPTAC Confirmation/Discovery cohort, distributions by proteome-based subtype. e For the top over-expressed proteins associated with each subtype (from part b, top panel), represented categories by GO were assessed, with selected enriched categories represented here. P-values by one-sided Fisher’s exact test. See also Supplementary Figs. 2–4 and Supplementary Data S2 and S3 and S4.
