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XPO1 Expression Is a Poor-Prognosis Marker in Pancreatic Adenocarcinoma

1
Laboratoire d’Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, F-13273 Marseille, France
2
Département d’Oncologie Médicale, Institut Paoli-Calmettes, F-13273 Marseille, France
3
Département de Chirurgie Générale et Viscérale, AP-HM, F-13000 Marseille, France
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 596; https://doi.org/10.3390/jcm8050596
Received: 1 April 2019 / Revised: 26 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
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Abstract

Pancreatic adenocarcinoma (PAC) is one of the most aggressive human cancers and new systemic therapies are urgently needed. Exportin-1 (XPO1), which is a member of the importin-β superfamily of karyopherins, is the major exporter of many tumor suppressor proteins that are involved in the progression of PAC. Promising pre-clinical data using XPO1 inhibitors have been reported in PAC, but very few data are available regarding XPO1 expression in clinical samples. Retrospectively, we analyzed XPO1 mRNA expression in 741 pancreatic samples, including 95 normal, 73 metastatic and 573 primary cancers samples, and searched for correlations with clinicopathological and molecular data, including overall survival. XPO1 expression was heterogeneous across the samples, higher in metastatic samples than in the primary tumors, and higher in primaries than in the normal samples. “XPO1-high” tumors were associated with positive pathological lymph node status and aggressive molecular subtypes. They were also associated with shorter overall survival in both uni- and multivariate analyses. Supervised analysis between the “XPO1-high” and “XPO1-low” tumors identified a robust 268-gene signature, whereby ontology analysis suggested increased XPO1 activity in the “XPO1-high” tumors. XPO1 expression refines the prognostication in PAC and higher expression exists in secondary versus primary tumors, which supports the development of XPO1 inhibitors in this so-lethal disease. View Full-Text
Keywords: pancreas cancer; prognosis; survival; XPO1 expression pancreas cancer; prognosis; survival; XPO1 expression
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Birnbaum, D.J.; Finetti, P.; Birnbaum, D.; Mamessier, E.; Bertucci, F. XPO1 Expression Is a Poor-Prognosis Marker in Pancreatic Adenocarcinoma. J. Clin. Med. 2019, 8, 596.

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