Michael Radmacher, PhD
Daniel Elgort, PhD
Oliver A. Hampton, PhD, MS
Phaedra Agius, PhD


We utilized Aster Insights’ clinicogenomic database to assess the prognostic significance of a signature of six immune-related genes in clear cell renal cell carcinoma first reported by Zhou et al in 2022. Our validation set was comprised of 1,060 clear cell renal cell carcinoma patients, each of whom had RNA-seq profiling of a sample collected from the primary tumor and associated longitudinal clinical data. In our validation set a risk score derived from the six-gene signature was an independent prognostic factor for overall survival in both univariate and multivariate modeling, the latter of which also considered age, sex, and stage, confirming findings in the original report. We were unable to definitively confirm the signature’s previously reported association with response to immunotherapy. In a subset of 163 patients from our cohort who started immune-checkpoint inhibitor therapy within five years of RNA-seq, we observed no association between risk score and response to immune checkpoint inhibitor therapy. There was, however, a marginal association between the risk score and real-world progression-free survival. Our study demonstrates the utility of Aster Insights’ real-world data for independent validation of reported gene expression signatures and their association with patient outcomes.

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