A nuclear shift of GSK3β protein is an independent prognostic factor in prostate cancer
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A nuclear shift of GSK3β protein is an independent prognostic factor in prostate cancer. / Eichenauer, Till; Hussein, Mohammad; Hube-Magg, Claudia; Kluth, Martina; Büscheck, Franziska; Höflmayer, Doris; Tsourlakis, Maria Christina; Steurer, Stefan; Clauditz, Till S; Luebke, Andreas M; Burandt, Eike; Wilczak, Waldemar; Hinsch, Andrea; Dum, David; Beyer, Burkhard; Steuber, Thomas; Huland, Hartwig; Graefen, Markus; Simon, Ronald; Sauter, Guido; Melling, Nathaniel; Schlomm, Thorsten; Minner, Sarah.
in: ONCOTARGET, Jahrgang 10, Nr. 18, 01.03.2019, S. 1729-1744.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A nuclear shift of GSK3β protein is an independent prognostic factor in prostate cancer
AU - Eichenauer, Till
AU - Hussein, Mohammad
AU - Hube-Magg, Claudia
AU - Kluth, Martina
AU - Büscheck, Franziska
AU - Höflmayer, Doris
AU - Tsourlakis, Maria Christina
AU - Steurer, Stefan
AU - Clauditz, Till S
AU - Luebke, Andreas M
AU - Burandt, Eike
AU - Wilczak, Waldemar
AU - Hinsch, Andrea
AU - Dum, David
AU - Beyer, Burkhard
AU - Steuber, Thomas
AU - Huland, Hartwig
AU - Graefen, Markus
AU - Simon, Ronald
AU - Sauter, Guido
AU - Melling, Nathaniel
AU - Schlomm, Thorsten
AU - Minner, Sarah
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Glycogen synthase kinase 3ß (GSK3ß) regulates many cancer relevant cellular processes and represents a potential therapeutic target. GSK3ß overexpression has been linked to adverse tumor features in many cancers, but its role in prostate cancer remains uncertain. We employed immunohistochemical GSK3ß expression analysis on a tissue microarray with 12,427 prostate cancers. Cytoplasmic and nuclear GSK3ß staining was separately analyzed. GSK3ß staining was absent in normal prostate epithelium, whereas 57% of 9,164 interpretable cancers showed detectable GSK3ß expression. Cytoplasmic staining was considered weak, moderate, and strong in 36%, 19.5% and 1.5% of tumors and was accompanied by nuclear GSK3ß staining in 47% of cases. Cytoplasmic GSK3ß staining as well as nuclear GSK3ß accumulation was associated with advanced tumor stage, high Gleason grade, presence of lymph node metastasis and early biochemical recurrence (p < 0.0001 each for cytoplasmic staining and nu-clear accumulation). Prognosis of GSK3ß positive cancers became particularly poor if nuclear GSK3ß staining was also seen (p < 0.0001). The prognostic impact of nuclear GSK3ß accumu-lation was independent of established preoperative and postoperative parameters in multivari-ate analyses (p < 0.0001). The significant association of GSK3ß expression with deletions of PTEN, 3p13 (p < 0.0001 each), 5q21 (p = 0.0014) and 6q15 (p = 0.0026) suggest a role of GSK3ß in the development of genomic instability. In summary, the results of our study identify GSK3ß as an independent prognostic marker in prostate cancer.
AB - Glycogen synthase kinase 3ß (GSK3ß) regulates many cancer relevant cellular processes and represents a potential therapeutic target. GSK3ß overexpression has been linked to adverse tumor features in many cancers, but its role in prostate cancer remains uncertain. We employed immunohistochemical GSK3ß expression analysis on a tissue microarray with 12,427 prostate cancers. Cytoplasmic and nuclear GSK3ß staining was separately analyzed. GSK3ß staining was absent in normal prostate epithelium, whereas 57% of 9,164 interpretable cancers showed detectable GSK3ß expression. Cytoplasmic staining was considered weak, moderate, and strong in 36%, 19.5% and 1.5% of tumors and was accompanied by nuclear GSK3ß staining in 47% of cases. Cytoplasmic GSK3ß staining as well as nuclear GSK3ß accumulation was associated with advanced tumor stage, high Gleason grade, presence of lymph node metastasis and early biochemical recurrence (p < 0.0001 each for cytoplasmic staining and nu-clear accumulation). Prognosis of GSK3ß positive cancers became particularly poor if nuclear GSK3ß staining was also seen (p < 0.0001). The prognostic impact of nuclear GSK3ß accumu-lation was independent of established preoperative and postoperative parameters in multivari-ate analyses (p < 0.0001). The significant association of GSK3ß expression with deletions of PTEN, 3p13 (p < 0.0001 each), 5q21 (p = 0.0014) and 6q15 (p = 0.0026) suggest a role of GSK3ß in the development of genomic instability. In summary, the results of our study identify GSK3ß as an independent prognostic marker in prostate cancer.
U2 - 10.18632/oncotarget.26739
DO - 10.18632/oncotarget.26739
M3 - SCORING: Journal article
C2 - 30899444
VL - 10
SP - 1729
EP - 1744
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 18
ER -