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PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma

Murnyák, Balázs; Kouhsari, Mahan C.; Hershkovitch, Rotem; Kálmán, Bernadette; Marko-Varga, György LU ; Klekner, Álmos and Hortobágyi, Tibor (2017) In Oncotarget 8(28). p.46348-46362
Abstract

Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of... (More)

Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p < 0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glioblastoma, Glioma, p53, PARP1
in
Oncotarget
volume
8
issue
28
pages
15 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85022209490
  • wos:000405504600114
ISSN
1949-2553
DOI
10.18632/oncotarget.18013
language
English
LU publication?
yes
id
11e6befd-2878-40b4-936f-a7697f8187f5
date added to LUP
2017-08-18 14:31:30
date last changed
2017-09-18 11:42:08
@article{11e6befd-2878-40b4-936f-a7697f8187f5,
  abstract     = {<p>Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p &lt; 0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM.</p>},
  author       = {Murnyák, Balázs and Kouhsari, Mahan C. and Hershkovitch, Rotem and Kálmán, Bernadette and Marko-Varga, György and Klekner, Álmos and Hortobágyi, Tibor},
  issn         = {1949-2553},
  keyword      = {Glioblastoma,Glioma,p53,PARP1},
  language     = {eng},
  number       = {28},
  pages        = {46348--46362},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma},
  url          = {http://dx.doi.org/10.18632/oncotarget.18013},
  volume       = {8},
  year         = {2017},
}