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The molecular basis for ethnic variation and histological subtype differences in prostate cancer.

ABSTRACT: Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data of prostate cancer genome also provide insights on ethnic variation and the differences in histological subtype of this disease. In this review, differences in the incidence of prostate cancer and the prevalence of main genetic alterations between Asian and Western populations are discussed. We also review the recent findings on the mechanisms underlying neuroendocrine differentiation of prostate cancer and the development of small cell neuroendocrine carcinoma after androgen deprivation therapy.

SUBMITTER: Zong Y

PROVIDER: S-EPMC4078990 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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The molecular basis for ethnic variation and histological subtype differences in prostate cancer.

Zong Yang Y Goldstein Andrew S AS Huang Jiaoti J

Science China. Life sciences 20130713 9

Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data ...[more]

PMID: 23852643

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Project description:Background and objectivesTranscriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation.Materials and methodsTo focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting.ResultsWe identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy.ConclusionWe propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.

Dataset Information

The molecular basis for ethnic variation and histological subtype differences in prostate cancer.

Publications

The molecular basis for ethnic variation and histological subtype differences in prostate cancer.

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