Transcriptional landscape of PTEN loss in primary prostate cancer

Eddie Luidy Imada*, Diego Fernando Sanchez, Wikum Dinalankara, Thiago Vidotto, Ericka M. Ebot, Svitlana Tyekucheva, Gloria Regina Franco, Lorelei Ann Mucci, Massimo Loda, Edward Matthew Schaeffer, Tamara Lotan, Luigi Marchionni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number856
JournalBMC cancer
Volume21
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Meta-analysis
  • Non-coding RNA
  • PTEN deletion
  • PTEN loss
  • Prostate Cancer
  • lncRNA

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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