The clinical relevance of the Hippo pathway in pancreatic ductal adenocarcinoma
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The clinical relevance of the Hippo pathway in pancreatic ductal adenocarcinoma. / Drexler, Richard; Küchler, Mirco; Wagner, Kim C.; Reese, Tim; Feyerabend, Bernd; Kleine, Moritz; Oldhafer, Karl J.
In: J CANCER RES CLIN, Vol. 147, No. 2, 24.02.2021, p. 373-391.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The clinical relevance of the Hippo pathway in pancreatic ductal adenocarcinoma
AU - Drexler, Richard
AU - Küchler, Mirco
AU - Wagner, Kim C.
AU - Reese, Tim
AU - Feyerabend, Bernd
AU - Kleine, Moritz
AU - Oldhafer, Karl J.
PY - 2021/2/24
Y1 - 2021/2/24
N2 - PURPOSE: The Hippo pathway has broadened in cancer research in the past decade and revealed itself to be an important driver for tumorigenesis and metastatic spread. In this study, we investigated the clinical relevance of the Hippo pathway with regard to metastatic invasion, patients' outcome and histopathological features.METHODS: Protein expression of components of the Hippo pathway were analyzed by immunohistochemistry (IHC) using paraffin-embedded tissue from 103 patients who had been diagnosed with pancreatic ductal adenocarcinoma and had undergone surgery. Results were correlated with clinicopathological data, disease-free and overall survival.RESULTS: Immunohistochemistry studies in pancreatic tumour tissues revealed a significant upregulation of MST1, MST2, pLATS, pYAP and 14-3-3, representing the active Hippo pathway, in non-metastasized patients (p < 0.01). In turn, the pathway is more inactive in metastasized patients and relating liver metastases as LATS1, LATS2, YAP, transcriptional factors TEAD2 and TEAD3 were upregulated in these patients (p < 0.01). A higher pYAP expression was associated with a favorable OS and DFS.CONCLUSION: The Hippo pathway is inactive in metastasized patients releasing the pro-metastatic and proliferative potential of the pathway. Furthermore, our study underlines the prognostic relevance of the Hippo pathway as a shift in the balance towards the inactive pathway predicts an unfavorable OS and DFS.
AB - PURPOSE: The Hippo pathway has broadened in cancer research in the past decade and revealed itself to be an important driver for tumorigenesis and metastatic spread. In this study, we investigated the clinical relevance of the Hippo pathway with regard to metastatic invasion, patients' outcome and histopathological features.METHODS: Protein expression of components of the Hippo pathway were analyzed by immunohistochemistry (IHC) using paraffin-embedded tissue from 103 patients who had been diagnosed with pancreatic ductal adenocarcinoma and had undergone surgery. Results were correlated with clinicopathological data, disease-free and overall survival.RESULTS: Immunohistochemistry studies in pancreatic tumour tissues revealed a significant upregulation of MST1, MST2, pLATS, pYAP and 14-3-3, representing the active Hippo pathway, in non-metastasized patients (p < 0.01). In turn, the pathway is more inactive in metastasized patients and relating liver metastases as LATS1, LATS2, YAP, transcriptional factors TEAD2 and TEAD3 were upregulated in these patients (p < 0.01). A higher pYAP expression was associated with a favorable OS and DFS.CONCLUSION: The Hippo pathway is inactive in metastasized patients releasing the pro-metastatic and proliferative potential of the pathway. Furthermore, our study underlines the prognostic relevance of the Hippo pathway as a shift in the balance towards the inactive pathway predicts an unfavorable OS and DFS.
UR - https://doi.org/10.1007/s00432-020-03427-z
U2 - 10.1007/s00432-020-03427-z
DO - 10.1007/s00432-020-03427-z
M3 - SCORING: Journal article
VL - 147
SP - 373
EP - 391
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 2
ER -
