Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
Standard
Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer. / Freytag, Morton; Kluth, Martina; Bady, Elena; Hube-Magg, Claudia; Makrypidi-Fraune, Georgia; Heinzer, Hans; Höflmayer, Doris; Weidemann, Sören; Uhlig, Ria; Huland, Hartwig; Graefen, Markus; Bernreuther, Christian; Wittmer, Corinna; Tsourlakis, Maria Christina; Minner, Sarah; Dum, David; Hinsch, Andrea; Luebke, Andreas M; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Möller, Katharina.
In: BMC CANCER, Vol. 20, No. 1, 18.12.2020, p. 1220.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
AU - Freytag, Morton
AU - Kluth, Martina
AU - Bady, Elena
AU - Hube-Magg, Claudia
AU - Makrypidi-Fraune, Georgia
AU - Heinzer, Hans
AU - Höflmayer, Doris
AU - Weidemann, Sören
AU - Uhlig, Ria
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Bernreuther, Christian
AU - Wittmer, Corinna
AU - Tsourlakis, Maria Christina
AU - Minner, Sarah
AU - Dum, David
AU - Hinsch, Andrea
AU - Luebke, Andreas M
AU - Simon, Ronald
AU - Sauter, Guido
AU - Schlomm, Thorsten
AU - Möller, Katharina
PY - 2020/12/18
Y1 - 2020/12/18
N2 - BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.METHODS: A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2.RESULTS: Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features.CONCLUSIONS: Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.
AB - BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.METHODS: A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2.RESULTS: Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features.CONCLUSIONS: Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.
U2 - 10.1186/s12885-020-07682-8
DO - 10.1186/s12885-020-07682-8
M3 - SCORING: Journal article
C2 - 33339518
VL - 20
SP - 1220
JO - BMC CANCER
JF - BMC CANCER
SN - 1471-2407
IS - 1
ER -
