Transcriptional landscape of PTEN loss in primary prostate cancer.

TitleTranscriptional landscape of PTEN loss in primary prostate cancer.
Publication TypeJournal Article
Year of Publication2021
AuthorsImada ELuidy, Sanchez DFernando, Dinalankara W, Vidotto T, Ebot EM, Tyekucheva S, Franco GRegina, Mucci LAnn, Loda M, Schaeffer EMatthew, Lotan T, Marchionni L
JournalBMC Cancer
Date Published2021 Jul 26
KeywordsAdaptive Immunity, Biomarkers, Tumor, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunity, Innate, Immunohistochemistry, Male, Prostatic Neoplasms, PTEN Phosphohydrolase, Transcriptional Regulator ERG, Transcriptome

BACKGROUND: PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa.

METHODS: Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas.

RESULTS: The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression.

CONCLUSION: We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

Alternate JournalBMC Cancer
PubMed ID34311724
PubMed Central IDPMC8314517
Grant ListR01CA200859 / CA / NCI NIH HHS / United States
U01CA196390 / CA / NCI NIH HHS / United States
W81XWH-16-1-0737 / / U.S. Department of Defense (US) /
W81XWH-16-1-0739 / / U.S. Department of Defense /
BDS-00493-16 / / Fundação de Amparo à Pesquisa do Estado de Minas Gerais (BR) /
Related Faculty: 
Luigi Marchionni, M.D., Ph.D. Massimo Loda, M.D.

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