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Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()

Rapid advances in the discovery of long noncoding RNAs (lncRNAs) have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa). Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prosta...

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Autores principales: Shukla, Sudhanshu, Zhang, Xiang, Niknafs, Yashar S., Xiao, Lanbo, Mehra, Rohit, Cieślik, Marcin, Ross, Ashley, Schaeffer, Edward, Malik, Bhavna, Guo, Shuling, Freier, Susan M., Bui, Huynh-Hoa, Siddiqui, Javed, Jing, Xiaojun, Cao, Xuhong, Dhanasekaran, Saravana M., Feng, Felix Y., Chinnaiyan, Arul M., Malik, Rohit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018094/
https://www.ncbi.nlm.nih.gov/pubmed/27566105
http://dx.doi.org/10.1016/j.neo.2016.07.001
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author Shukla, Sudhanshu
Zhang, Xiang
Niknafs, Yashar S.
Xiao, Lanbo
Mehra, Rohit
Cieślik, Marcin
Ross, Ashley
Schaeffer, Edward
Malik, Bhavna
Guo, Shuling
Freier, Susan M.
Bui, Huynh-Hoa
Siddiqui, Javed
Jing, Xiaojun
Cao, Xuhong
Dhanasekaran, Saravana M.
Feng, Felix Y.
Chinnaiyan, Arul M.
Malik, Rohit
author_facet Shukla, Sudhanshu
Zhang, Xiang
Niknafs, Yashar S.
Xiao, Lanbo
Mehra, Rohit
Cieślik, Marcin
Ross, Ashley
Schaeffer, Edward
Malik, Bhavna
Guo, Shuling
Freier, Susan M.
Bui, Huynh-Hoa
Siddiqui, Javed
Jing, Xiaojun
Cao, Xuhong
Dhanasekaran, Saravana M.
Feng, Felix Y.
Chinnaiyan, Arul M.
Malik, Rohit
author_sort Shukla, Sudhanshu
collection PubMed
description Rapid advances in the discovery of long noncoding RNAs (lncRNAs) have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa). Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA) and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126), PSS (P = .0385), and MFS (P = .000609), with trends for OS as well (P = .056). An RNA in-situ hybridization (ISH) assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.
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spelling pubmed-50180942016-09-16 Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer() Shukla, Sudhanshu Zhang, Xiang Niknafs, Yashar S. Xiao, Lanbo Mehra, Rohit Cieślik, Marcin Ross, Ashley Schaeffer, Edward Malik, Bhavna Guo, Shuling Freier, Susan M. Bui, Huynh-Hoa Siddiqui, Javed Jing, Xiaojun Cao, Xuhong Dhanasekaran, Saravana M. Feng, Felix Y. Chinnaiyan, Arul M. Malik, Rohit Neoplasia Article Rapid advances in the discovery of long noncoding RNAs (lncRNAs) have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa). Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA) and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126), PSS (P = .0385), and MFS (P = .000609), with trends for OS as well (P = .056). An RNA in-situ hybridization (ISH) assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence. Neoplasia Press 2016-09-09 /pmc/articles/PMC5018094/ /pubmed/27566105 http://dx.doi.org/10.1016/j.neo.2016.07.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Shukla, Sudhanshu
Zhang, Xiang
Niknafs, Yashar S.
Xiao, Lanbo
Mehra, Rohit
Cieślik, Marcin
Ross, Ashley
Schaeffer, Edward
Malik, Bhavna
Guo, Shuling
Freier, Susan M.
Bui, Huynh-Hoa
Siddiqui, Javed
Jing, Xiaojun
Cao, Xuhong
Dhanasekaran, Saravana M.
Feng, Felix Y.
Chinnaiyan, Arul M.
Malik, Rohit
Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title_full Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title_fullStr Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title_full_unstemmed Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title_short Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer()
title_sort identification and validation of pcat14 as prognostic biomarker in prostate cancer()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018094/
https://www.ncbi.nlm.nih.gov/pubmed/27566105
http://dx.doi.org/10.1016/j.neo.2016.07.001
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