Association of subcellular localization of TEAD transcription factors with outcome and progression in pancreatic ductal adenocarcinoma
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Association of subcellular localization of TEAD transcription factors with outcome and progression in pancreatic ductal adenocarcinoma. / Drexler, Richard; Fahy, Rebecca; Küchler, Mirco; Wagner, Kim C.; Reese, Tim; Ehmke, Mareike; Feyerabend, Bernd; Kleine, Moritz; Oldhafer, Karl J.
in: PANCREATOLOGY, Jahrgang 21, Nr. 1, 01.2021, S. 170-179.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association of subcellular localization of TEAD transcription factors with outcome and progression in pancreatic ductal adenocarcinoma
AU - Drexler, Richard
AU - Fahy, Rebecca
AU - Küchler, Mirco
AU - Wagner, Kim C.
AU - Reese, Tim
AU - Ehmke, Mareike
AU - Feyerabend, Bernd
AU - Kleine, Moritz
AU - Oldhafer, Karl J.
PY - 2021/1
Y1 - 2021/1
N2 - BackgroundTranscriptional enhanced associated domain (TEAD) transcription factors are nuclear effectors of several oncogenic signalling pathways including Hippo, WNT, TGF-ß and EGFR pathways that interact with various cancer genes. The subcellular localization of TEAD regulates the functional output of these pathways affecting tumour progression and patient outcome. However, the impact of the TEAD family on pancreatic ductal adenocarcinoma (PDAC) and its clinical progression remain elusive.MethodsA cohort of 81 PDAC patients who had undergone surgery was established. Cytoplasmic and nuclear localization of TEAD1, TEAD2, TEAD3 and TEAD4 was evaluated with the immunoreactive score (IRS) by immunohistochemistry (IHC) using paraffin-embedded tissue. Results were correlated with clinicopathological data, disease-free and overall survival.ResultsNuclear staining of all four TEADs was increased in pancreatic cancer tissue. Patients suffering from metastatic disease at time of surgery showed a strong nuclear staining of TEAD2 and TEAD3 (p < 0.05). Furthermore, a nuclear > cytoplasmic ratio of TEAD2 and TEAD3 was associated with a shorter overall survival and TEAD2 emerged as an independent prognostic factor for disease-free survival.ConclusionOur study underlines the importance of TEAD transcription factors in PDAC as a nuclear localization was found to be associated with metastatic disease and an unfavourable prognosis after surgical resection.
AB - BackgroundTranscriptional enhanced associated domain (TEAD) transcription factors are nuclear effectors of several oncogenic signalling pathways including Hippo, WNT, TGF-ß and EGFR pathways that interact with various cancer genes. The subcellular localization of TEAD regulates the functional output of these pathways affecting tumour progression and patient outcome. However, the impact of the TEAD family on pancreatic ductal adenocarcinoma (PDAC) and its clinical progression remain elusive.MethodsA cohort of 81 PDAC patients who had undergone surgery was established. Cytoplasmic and nuclear localization of TEAD1, TEAD2, TEAD3 and TEAD4 was evaluated with the immunoreactive score (IRS) by immunohistochemistry (IHC) using paraffin-embedded tissue. Results were correlated with clinicopathological data, disease-free and overall survival.ResultsNuclear staining of all four TEADs was increased in pancreatic cancer tissue. Patients suffering from metastatic disease at time of surgery showed a strong nuclear staining of TEAD2 and TEAD3 (p < 0.05). Furthermore, a nuclear > cytoplasmic ratio of TEAD2 and TEAD3 was associated with a shorter overall survival and TEAD2 emerged as an independent prognostic factor for disease-free survival.ConclusionOur study underlines the importance of TEAD transcription factors in PDAC as a nuclear localization was found to be associated with metastatic disease and an unfavourable prognosis after surgical resection.
UR - https://doi.org/10.1016/j.pan.2020.12.003
U2 - 10.1016/j.pan.2020.12.003
DO - 10.1016/j.pan.2020.12.003
M3 - SCORING: Journal article
VL - 21
SP - 170
EP - 179
JO - PANCREATOLOGY
JF - PANCREATOLOGY
SN - 1424-3903
IS - 1
ER -