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Open Access 01-12-2021 | Prostate Cancer | Research article

Transcriptional landscape of PTEN loss in primary prostate cancer

Authors: 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

Published in: BMC Cancer | Issue 1/2021

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.

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Title: Transcriptional landscape of PTEN loss in primary prostate cancer
Authors: 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
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Prostate Cancer
Prostate Cancer
Androgens
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08593-y

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

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Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer