Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer

Gloria Regina Franco¹  Ericka M. Ebot²  Lorelei Ann Mucci²  Svitlana Tyekucheva²  Diego Fernando Sanchez³  Tamara Lotan⁴  Massimo Loda⁵  Luigi Marchionni⁶  Wikum Dinalankara⁶  Eddie Luidy Imada⁷  Thiago Vidotto⁸  Edward Matthew Schaeffer⁹ 

[1] Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA;Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA;Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA;Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Urology, Northwestern University, Evanston, IL, USA;

关键词: Prostate Cancer;    PTEN deletion;    PTEN loss;    Non-coding RNA;    lncRNA;    Meta-analysis;   

DOI  :  10.1186/s12885-021-08593-y

来源: Springer

【 摘 要 】

BackgroundPTEN 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.MethodsUsing 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.ResultsThe 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.ConclusionWe 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.

【 授权许可】

CC BY