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Fig. 1 | BMC Cancer

Fig. 1

From: Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma

Fig. 1

Gene signature scores across datasets profiling NEPC and adenocarcinomas. (A[A’]:B[B’]) denotes cohort sizes of A adenocarcinomas and B NEPCs including A’ or B’ adenocarcinomas with NE differentiation, u denotes mean score of the adenocarcinoma cohort, p denotes p-value under t-test comparison of NEPCs versus adenocarcinomas, and (*) signifies p-values after averaging over multiple samples from the same patient. ARS and neuronal phenotype scores completely separated cohorts (AUC 100%) in xenograft and frozen tissue primary datasets (Lucap-x, VPC-x, MDA-x, MDA), and ARS demonstrated significant cohort differences (p<0.05) across all datasets. CCP was highly correlated to an RB loss signature (mean r=0.96 across datasets; not shown), in agreement with reports showing correlation of CCP and E2F1 targets [7]. In UW, NEPCs annotated as adenocarcinomas with NE differentiation mostly demonstrated ARS and CCP scores similar to adenocarcinomas. In WCMC and SU2C, NEPCs also sometimes demonstrated gene signature scores similar to adenocarcinomas, and may have corresponded to adenocarcinomas with NE differentiation, however NEPC subtypes were not specified in annotations provided. In JHU-FFPE, 5 SCPCs exhibited ARS scores similar to adenocarcinomas (fold-change > -0.5 and z-score > -1), and are investigated further in the JHU-FPE results section. JHU-FFPE scores also demonstrated the least dynamic range across gene signatures, likely related to RNA degradation in FFPE. Gene signature scores were formed by average expression of genes. Among single-sample scoring methods, SVD-based PLAGE has been recognized as a top performer and is equivalent to (signed) average expression for perfectly correlated (and anti-correlated) genes. Indeed, PLAGE and average expression were highly correlated across the NEPC datasets (correlations for CCP > 0.99, Neuronal > 0.96, ARS > 0.95)

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