Researchers say they have identified 4 subtypes of prostate cancer with distinct biological and clinical features, and these subtypes may respond differently to treatment.

The subtypes were identified by analyzing the gene expression profiles of more than 100,000 prostate tumors. The researchers reported their findings in Cancer.

The team analyzed gene expression profiles from 32,000 tumors as the training set and 68,547 tumors for the evaluation set. 

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Four distinct prostate cancer subtypes were identified — luminal differentiated, luminal proliferating, basal immune, and basal neuroendocrine.

The luminal subtypes had higher levels of androgen receptor transcriptional activity, higher expression of prostate-specific membrane antigen, and greater expression of prostate luminal genes. 

The luminal proliferating subtype had higher levels of the hallmark for PI3K/mTOR activity and tended to have characteristics of homologous recombination deficiency. MYC activity signature 1, which is enriched with cell-cycle and DNA repair genes, was higher in this subtype. 

Patients with the luminal differentiated subtype tended to have lower-grade, organ-confined disease. Luminal differentiated tumors also had “cancer hallmarks associated with a higher degree of cellular differentiation, more similar to nonneoplastic luminal cells,” the researchers noted.

Basal neuroendocrine tumors were most common in Asian and Black patients. MYC activity signature 2, which is enriched with genes involved in RNA processing and ribosomal biogenesis, was higher in this subtype.  

The basal immune subtype had higher levels of tumor-infiltrating lymphocytes and interferon gamma activity. Characteristics of homologous recombination deficiency were more common in tumors of this subtype.

The researchers also found that treatment outcomes differed across the subtypes. 

In one cohort, the addition of docetaxel to androgen deprivation therapy improved overall survival in patients with the luminal proliferating subtype (hazard ratio [HR], 0.21; 95% CI, 0.09-0.51) but not the luminal differentiated subtype (HR, 0.80; 95% CI, 0.49-1.32). 

In another cohort, adjuvant radiation after prostatectomy improved metastasis-free survival for patients with the basal immune subtype (HR, 0.09; 95% CI, 0.01-0.71) but none of the other subtypes.

The researchers noted, however, that prospective studies are needed to confirm whether this classification is predictive of treatment response.

Disclosures: This research was partly supported by Veracyte, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Weiner AB, Liu Y, Hakansson A, et al. A novel prostate cancer subtyping classifier based on luminal and basal phenotypes. Cancer. Published online April 14, 2023. doi:10.1002/cncr.34790

This article originally appeared on Cancer Therapy Advisor