Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma

Mohammed Alshalalfa, Yang Liu, Alexander W. Wyatt, Ewan A. Gibb, Harrison K. Tsai, Nicholas Erho, Jonathan Lehrer, Mandeep Takhar, Varune R. Ramnarine, Colin C. Collins, Robert B. Den, Edward M. Schaeffer, Elai Davicioni, Tamara Lotan, Tarek A. Bismar

Research output: Contribution to journalArticle

Abstract

Prostatic small cell neuroendocrine carcinoma (SC/NE) is well studied in metastatic castration-resistant prostate cancer; however, it is not well characterized in the primary setting. Herein, we used gene expression profiling of SC/NE prostate cancer (PCa) to develop a 212 gene signature to identify treatment-naïve primary prostatic tumors that are molecularly analogous to SC/NE (SC/NE-like PCa). The 212 gene signature was tested in several cohorts confirming similar molecular profile between prostatic SC/NE and small cell lung carcinoma. The signature was then translated into a genomic score (SCGScore) using modularized logistic regression modeling and validated in four independent cohorts achieving an average AUC >0.95. The signature was evaluated in more than 25,000 primary adenocarcinomas to characterize the biology, prognosis and potential therapeutic response of predicted SC/NE-like tumors. Assessing SCGScore in a prospective cohort of 17,967 RP and 6,697 biopsy treatment-naïve primary tumors from the Decipher Genomic Resource Information Database registry, approximately 1% of the patients were found to have a SC/NE-like transcriptional profile, whereas 0.5 and 3% of GG1 and GG5 patients respectively showed to be SC/NE-like. More than 80% of these patients are genomically high-risk based on Decipher score. Interrogating in vitro drug sensitivity analyses, SC/NE-like prostatic tumors showed higher response to PARP and HDAC inhibitors.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StatePublished - Jan 1 2019

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Neuroendocrine Carcinoma
Small Cell Carcinoma
Prostatic Neoplasms
Neoplasms
Histone Deacetylase Inhibitors
Castration
Small Cell Lung Carcinoma
Gene Expression Profiling
Genes
Area Under Curve
Registries
Adenocarcinoma
Therapeutics
Logistic Models
Databases
Biopsy

Keywords

  • drug sensitivity
  • localized
  • molecular signature
  • neuroendocrine prostate cancer
  • SC/NE-like

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma. / Alshalalfa, Mohammed; Liu, Yang; Wyatt, Alexander W.; Gibb, Ewan A.; Tsai, Harrison K.; Erho, Nicholas; Lehrer, Jonathan; Takhar, Mandeep; Ramnarine, Varune R.; Collins, Colin C.; Den, Robert B.; Schaeffer, Edward M.; Davicioni, Elai; Lotan, Tamara; Bismar, Tarek A.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Alshalalfa, M, Liu, Y, Wyatt, AW, Gibb, EA, Tsai, HK, Erho, N, Lehrer, J, Takhar, M, Ramnarine, VR, Collins, CC, Den, RB, Schaeffer, EM, Davicioni, E, Lotan, T & Bismar, TA 2019, 'Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma', International Journal of Cancer. https://doi.org/10.1002/ijc.32430
Alshalalfa, Mohammed ; Liu, Yang ; Wyatt, Alexander W. ; Gibb, Ewan A. ; Tsai, Harrison K. ; Erho, Nicholas ; Lehrer, Jonathan ; Takhar, Mandeep ; Ramnarine, Varune R. ; Collins, Colin C. ; Den, Robert B. ; Schaeffer, Edward M. ; Davicioni, Elai ; Lotan, Tamara ; Bismar, Tarek A. / Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma. In: International Journal of Cancer. 2019.
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AU - Tsai, Harrison K.

AU - Erho, Nicholas

AU - Lehrer, Jonathan

AU - Takhar, Mandeep

AU - Ramnarine, Varune R.

AU - Collins, Colin C.

AU - Den, Robert B.

AU - Schaeffer, Edward M.

AU - Davicioni, Elai

AU - Lotan, Tamara

AU - Bismar, Tarek A.

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