Transcriptomic Profiling Offers Neoadjuvant Therapy Benefits for PCa

By Emily Menendez - April 12, 2023

The utilization of transcriptomic profiling for diseases such as prostate cancer allows researchers to focus on a set of relevant target genes and transcripts under various conditions. Transcriptomic profiling was used in a recent study to identify the predictive biomarkers for neoadjuvant therapy and determine the accurate responses of patients treated with docetaxel-based neoadjuvant chemohormonal therapy (NCHT) and neoadjuvant hormonal therapy (NHT).

Previous studies have shown that patients with locally advanced prostate cancer (LAPCa) who received docetaxel-based NCHT had better outcomes after surgery than patients who were treated with NHT. Not all patients treated with NCHT experienced favorable clinical outcomes, however, leading to the need for a potential biomarker assessment.

Transcriptomic profiling was performed on baseline biopsies and tissue specimens from 64 patients with LAPCa at Renji Hospital in China between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to find predictive biomarkers to guide treatment selection.

The transcriptome profiling of pre- and posttreatment LAPCa specimens was compared, with results showing that NCHT and NHT shared 1917 up-regulated and 670 down-regulated differentially expressed genes at least 2-fold. A pathway enrichment analysis showed that up-regulated pathways in response to NCHT and NHT were both enriched in cytokine receptor interaction pathways, while down-regulated pathways in response to NCHT were enriched in cell cycle pathways.

Through the comprehensive transcriptome profiling of all 64 baseline specimens, 10 predictive markers were identified and integrated into the signature to determine the benefits of neoadjuvant therapy, which categorizes patients into 2 subgroups with relative bPFS benefits from either NHCT or NHT. In the high score (≥ –95.798) group (n=37), NCHT treatment led to significantly longer bPFS (P<.0001), with a clear and early separation of the Kaplan-Meier curves. In the low score (< –95.798) group (n=27), NHT also led to significantly longer bPFS (P=.0025).

The study determined that the first predictive transcriptomic signature may effectively guide the selection of neoadjuvant therapy for LAPCa and can provide guidance for personalized adjuvant therapy.