Introduction:

Genomic classifiers are increasingly utilized for prostate cancer (PCa) risk stratification. Clinico-pathologic differences in Gleason score, adverse pathology, and biochemical recurrence exist between PCa of the transition zone (TZ) and peripheral zone (PZ). There is no published data comparing Decipher scores from PCa of the TZ vs. PZ. In addition, the transcriptomic zonal differences of PCa remain unknown. We aimed to compare Decipher score and transcriptomics between PCa arising from TZ and PZ.

Methods:

There were 112 patients (113 samples) who received clinical Decipher testing between 2015-2023 from an MRI positive lesion on fusion biopsy. Decipher, pathology, and MRI were manually reviewed to identify zonal location of tissue sent for Decipher. Statistical analysis included t-tests, chi-squared, and multivariable linear regression where appropriate. Differential gene expression analysis was performed on Decipher microarray data. Nominal p-value cutoff of 0.001 was used to select significantly differentially expressed genes. The NIH DAVID was used for gene pathway analysis.

Results:

There were 32 TZ and 81 PZ samples and there were no differences in baseline patient characteristics. There were differences (Table 1, p <0.05) in Decipher score, target lesion size, and specimen type (RP or biopsy) between groups. On multivariable analysis, Decipher zonal location (PZ or TZ) and target lesion size were independently associated with Decipher score. 222 genes were differentially expressed between TZ and PZ lesions with enrichment of genes implicated in metabolic reprogramming and cell differentiation. Several genes, including FOXF2 and SOX2, are well described in literature as functionally important in PCa and were differentially expressed between the zonal locations (Figure).

Conclusion:

TZ PCa lesions were larger and had lower Decipher scores compared to PZ lesions. Gene expression differences exist between TZ and PZ lesions that represent key oncogenic pathways in metabolism and cell differentiation. Our findings highlight potential biologic differences between PCa of the PZ and TZ which merits further investigation.

Funding: N/A