# A Novel Molecular Profile of Hormone‐Sensitive Prostate Cancer Defines High Risk Patients

## TL;DR

This study identifies a genetic profile in hormone-sensitive prostate cancer that helps distinguish high-risk patients and suggests new treatment targets.

## Contribution

The study discovers a novel gene expression signature in metastatic hormone-sensitive prostate cancer that could guide personalized treatment.

## Key findings

- 42 genes showed differential expression between high- and low-risk prostate cancer patients.
- AKT2 and other genes related to apoptosis, PI3K, and MAPK pathways were overexpressed in high-risk patients.
- The identified genetic signature suggests potential new therapeutic targets like AKT2.

## Abstract

The therapeutic management of metastatic hormone‐sensitive prostate cancer (mHSPC) is still based on clinical and pathological parameters due to the lack of biomarkers that may drive tailored treatment.

In this non‐randomized, single‐center, retrospective trial, we searched for a genetic signature using the NanoString nCounter PanCancer Pathways Panel on formalin‐fixed paraffin embedded prostate cancer samples belonging to 48 patients with de novo or relapsed mHSPC. Patients were divided into a high‐clinical‐risk group (n = 36) and a low‐clinical‐risk group (n = 12) according to the mean time to metastatic relapse.

The analysis of Nanostring nCounter Panel data revealed differential expression of 42 genes between high‐clinical‐risk and low‐clinical‐risk groups. All the genes except for NR4A1 and FOS were upregulated in the high‐clinical‐risk group. A general overexpression of apoptosis, PI3K and MAPK pathway‐related genes, including AKT2, was observed in the high‐clinical‐risk group.

The differential genetic signature identified between the two study groups revealed novel biomarkers in mHSPC, additionally suggesting new therapeutic targets within the hormone sensitive phase, such as AKT2. Further prospective larger cohort studies are needed to assess the prognostic value of our findings and their exact role in prostate cancer progression.