scholarly journals Transcriptional landscape of PTEN loss in primary prostate cancer

2020 ◽  
Author(s):  
Eddie Luidy Imada ◽  
Diego Fernando Sanchez ◽  
Wikum Dinalankara ◽  
Thiago Vidotto ◽  
Ericka M Ebot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Pten Loss ◽  
Adaptive Immune ◽  
Primary Prostate Cancer ◽  
Expression Atlas ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
Adaptive Immune Systems ◽  
Transcriptional Landscape

ABSTRACTPTEN 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. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. Strikingly, the signature indicates 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. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape of PTEN loss in PCa that comprises both the coding and an extensive non-coding counterpart.

scholarly journals Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eddie Luidy Imada ◽  
Diego Fernando Sanchez ◽  
Wikum Dinalankara ◽  
Thiago Vidotto ◽  
Ericka M. Ebot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Pten Loss ◽  
Primary Prostate Cancer ◽  
Expression Atlas ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
New Biomarkers ◽  
Adaptive Immune Systems ◽  
Transcriptional Landscape

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.

Comparison of PET/MRI with multiparametric MRI in diagnosis of primary prostate cancer: A meta-analysis

2019 ◽  
Vol 113 ◽  
pp. 225-231 ◽  
Author(s):  
Mou Li ◽  
Zixing Huang ◽  
Haopeng Yu ◽  
Yi Wang ◽  
Yongchang Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Multiparametric Mri ◽  
Primary Prostate Cancer

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

2019 ◽  
Vol 145 (12) ◽  
pp. 3453-3461 ◽  
Author(s):  
Mohammed Alshalalfa ◽  
Yang Liu ◽  
Alexander W. Wyatt ◽  
Ewan A. Gibb ◽  
Harrison K. Tsai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Carcinoma ◽  
Small Cell ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Primary Prostate Cancer ◽  
Transcriptomic Signature

scholarly journals The epigenetic and transcriptional landscape of neuroendocrine prostate cancer

2020 ◽  
Vol 27 (2) ◽  
pp. R35-R50 ◽  
Author(s):  
Alastair Davies ◽  
Amina Zoubeidi ◽  
Luke A Selth
Keyword(s):  
Prostate Cancer ◽  
Transcriptional Networks ◽  
Oncogenic Signaling ◽  
Altered Expression ◽  
Modifying Factors ◽  
Neuroendocrine Prostate Cancer ◽  
Lineage Reprogramming ◽  
Transcriptional Changes ◽  
Aberrant Dna Methylation ◽  
Transcriptional Landscape

Tumours adapt to increasingly potent targeted therapies by transitioning to alternative lineage states. In prostate cancer, the widespread clinical application of androgen receptor (AR) pathway inhibitors has led to the insurgence of tumours relapsing with a neuroendocrine phenotype, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests that this lineage reprogramming is driven largely by dysregulation of the epigenome and transcriptional networks. Indeed, aberrant DNA methylation patterning and altered expression of epigenetic modifiers, such as EZH2, transcription factors, and RNA-modifying factors, are hallmarks of NEPC tumours. In this review, we explore the nature of the epigenetic and transcriptional landscape as prostate cancer cells lose their AR-imposed identity and transition to the neuroendocrine lineage. Beyond addressing the mechanisms underlying epithelial-to-neuroendocrine lineage reprogramming, we discuss how oncogenic signaling and metabolic shifts fuel epigenetic/transcriptional changes as well as the current state of epigenetic therapies for NEPC.

scholarly journals Identification of potential biomarkers associated with pathogenesis of primary prostate cancer based on meta-analysis approaches

2020 ◽  
Author(s):  
Neda Sepahi ◽  
Mehrdad Piran ◽  
Mehran Piran ◽  
Ali Ghanbariasad
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Incidence Rates ◽  
P Value ◽  
Diagnosis And Prognosis ◽  
Gene Ontology Database ◽  
Primary Prostate Cancer ◽  
Rising Incidence ◽  
Potential Biomarkers

AbstractWorldwide prostate cancer (PCa) is recognized as the second most common diagnosed cancer and the fifth leading cause of cancer death among men globally. Rising incidence rates of PCa have been observed over the last few decades. It is necessary to improve prostate cancer detection, diagnosis, treatment and survival. However, there are few reliable biomarkers for early prostate cancer diagnosis and prognosis. In the current study, systems biology method was applied for transcriptomic data analysis to identify potential biomarkers for primary PCa. We firstly identified differentially expressed genes (DEGs) between primary PCa and normal samples. Then the DEGs were mapped in Wikipathways and gene ontology database to conduct functional categories enrichment analysis. 1575 unique DEGs with adjusted p-value < 0.05 were achieved from two sets of DEGs. 132 common DEGs between two sets of DEGs were retrieved. The final DEGs were selected from 60 common upregulated and 72 common downregulated genes between datasets. In conclusion, we demonstrated some potential biomarkers (FOXA1, AGR2, EPCAM, CLDN3, ERBB3, GDF15, FHL1, NPY, DPP4, and GADD45A) and HIST2H2BE as a candidate one which are tightly correlated with the pathogenesis of PCa.

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