Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors
Por:
Gil J., Marques-Pamies M., Valassi E., Serra G., Salinas I., Xifra G., Casano-Sancho P., Carrato C., Biagetti B., Sesmilo G., Marcos-Ruiz J., Rodriguez-Lloveras H., Rueda-Pujol A., Aulinas A., Blanco A., Hostalot C., Simó-Servat A., Munoz, F, Rico M., Ibanez-Dominguez, J, Cordero E., Webb S.M., Jordà M., Puig-Domingo M.
Publicada:
22 mar 2023
Ahead of Print:
22 mar 2023
Resumen:
IntroductionDifferent medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. MethodsWe aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. ResultsWe found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. ConclusionNF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET.
Filiaciones:
Gil J.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Univ Autonoma Barcelona, Hosp St Pau, Res Ctr Pituitary Dis, Dept Endocrinol,IIB SPau,Dept Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Red Enfermedades Raras, Unit 747, CIBERER, Madrid, Spain
Marques-Pamies M.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Hosp Municipal Badalona, Dept Endocrinol, Badalona, Catalonia, Spain
Valassi E.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Univ Autonoma Barcelona, Hosp St Pau, Res Ctr Pituitary Dis, Dept Endocrinol,IIB SPau,Dept Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Red Enfermedades Raras, Unit 747, CIBERER, Madrid, Spain
Serra G.:
Son Espases Univ Hosp, Dept Endocrinol, Palma De Mallorca, Spain
Salinas I.:
Germans Trias & Pujol Univ Hosp, Dept Endocrinol & Nutr, Badalona, Spain
Xifra G.:
Josep Trueta Univ Hosp, Dept Endocrinol, Girona, Spain
Casano-Sancho P.:
Univ Barcelona, Hosp St Joan Deu, Inst Recerca SJS 39 57, Ctr Invest Red Diabet & Enfermedades Metab Asocia, Esplugues, Spain
Carrato C.:
Germans Trias & Pujol Univ Hosp, Dept Pathol, Badalona, Spain
Biagetti B.:
Univ Hosp Vall Hebron, Dept Endocrinol, Barcelona, Spain
Sesmilo G.:
Dexeus Univ Hosp, Dept Endocrinol, Barcelona, Spain
Marcos-Ruiz J.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Rodriguez-Lloveras H.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Rueda-Pujol A.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Aulinas A.:
Univ Autonoma Barcelona, Hosp St Pau, Res Ctr Pituitary Dis, Dept Endocrinol,IIB SPau,Dept Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Red Enfermedades Raras, Unit 747, CIBERER, Madrid, Spain
Blanco A.:
Germans Trias & Pujol Univ Hosp, Dept Neurosurg, Badalona, Spain
Hostalot C.:
Germans Trias & Pujol Univ Hosp, Dept Neurosurg, Badalona, Spain
Simó-Servat A.:
Hosp Univ Mutua Terrassa, Dept Endocrinol, Terrassa, Spain
Munoz, F:
Hosp Santa Creu & Sant Pau, Dept Neurosurg, Barcelona, Spain
Rico M.:
Hosp Santa Creu & Sant Pau, Dept Neurosurg, Barcelona, Spain
Ibanez-Dominguez, J:
Son Espases Univ Hosp, Dept Neurosurg, Palma De Mallorca, Spain
Cordero E.:
Univ Hosp Vall Hebron, Dept Neurosurg, Barcelona, Spain
Webb S.M.:
Univ Autonoma Barcelona, Hosp St Pau, Res Ctr Pituitary Dis, Dept Endocrinol,IIB SPau,Dept Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Red Enfermedades Raras, Unit 747, CIBERER, Madrid, Spain
Jordà M.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Puig-Domingo M.:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Badalona, Spain
Inst Salud Carlos III, Ctr Invest Red Enfermedades Raras, Unit 747, CIBERER, Madrid, Spain
Hosp Municipal Badalona, Dept Endocrinol, Badalona, Catalonia, Spain
Green Published, gold, All Open Access, Gold, Green
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