Quantitative Biology

Tumour-Purity Adjustment of Published Prognostic Transcriptomic Signatures: A Pan-Cancer Audit in 12 TCGA Cohorts

Authors: Tianjiao Wang
Comments: 12 Pages.

Prognostic transcriptomic signatures are commonly evaluated in bulk tumour tissue, where measured expression reflects malignant cells together with stromal and immune compartments. Tumour purity may therefore be associated with both a signature score and survival, complicating the interpretation of an unadjusted prognostic coefficient. We conducted a pan-cancer audit of published prognostic transcriptomic signatures across 12 The Cancer Genome Atlas (TCGA) cohorts, examining how purity adjustment changes their associations with overall survival. The inventory comprised54 eligible published signatures, six reference gene sets, and two additional published signatures excluded for insufficient gene coverage. One included ovarian lncRNA signature could not be scored in its intended cohort because a component gene had zero variance,yielding 53 published signatures and six reference sets (59 distinct scored sets) across 129 signature—cohort pairs. The primary analysisincluded 5,417 patients and 1,939 deaths. After false-discovery-rate correction, 97 of 129 pairs showed an association between signature score and ABSOLUTE purity. The median absolute coefficient change after purity adjustment was 0.022; four pairs were classified as attenuated, 13 as amplified, and 112 as not distinguishablefrom zero. All four attenuated pairs were reference sets rather than published prognostic signatures. The magnitude and classificationof coefficient changes varied across purity estimators, highlighting the importance of estimator choice when evaluating prognostictranscriptomic signatures. These findings describe conditional associations and do not imply a causal effect of tumour purity.
Category: Quantitative Biology