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Researchers recently revealed the distinctive transcriptional profile of metastatic hormone-naïve prostate cancer, a critical resource for understanding mHNPC.

Metastatic hormone-naïve prostate cancer (mHNPC) is biologically and molecularly unique, according to a transcriptional analysis published online in Genome Biology.

“Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodeling as a predominant feature of these tumors,” wrote corresponding author Arkaitz Carracedo, PhD, of the Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance, and study coauthors.

Characterized by metastasis at the time of diagnosis, mHNPC is relatively uncommon yet accounts for up to half of deaths related to prostate cancer. Nevertheless, the molecular characteristics of mHNPC were largely unexplored prior to this study.

Advanced Computational Approach

Using bulk and single-cell RNA sequencing technologies, multiple research teams collaborated to investigate and present the first comprehensive transcriptome-wide characterization of primary tumors from patients with mHNPC.

“[A] detailed analysis of this type of tumor required accessing tissue archives from the past 10 years at Basurto Hospital, in order to obtain a sample size robust enough for analysis,” said researcher Ana Loizaga, PhD, of Basurto University Hospital, in a news release. “Moreover, we had to innovate within the clinical pathway to ensure that samples extracted from patients could be delivered to CIC bioGUNE within just a few hours.”

The advanced computational approach used in the study enabled the decomposition of primary tumor specimens into their cellular components, the research team explained.

“Most molecular studies treat the tumor as a homogeneous tissue, which limits our understanding of the disease,” said study co-leader Isabel Mendizabal, PhD, of CIC bioGUNE. “In this study, we complemented that approach with new technologies that allow us to analyze each cancer component in isolation, like tasting each fruit in a smoothie individually, instead of guessing the ingredients.”

Profound Understanding of mHNPC

The study revealed the distinctiveness of mHNPC. Cancer cells in mHNPC tumors, the team found, trigger a type of heterotypic communication associated with the acquisition of metastatic properties that benefit the tumor.

“We observed that the aggressiveness of this disease is partly due to how cancer cells ‘educate’ normal cells, through mechanisms we had not seen before,” said Dr. Carracedo.

The findings offer the most comprehensive transcriptional portrait of mHNPC available.

“Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management,” the researchers wrote.