Pancreatic endocrine tumors

Expression profiling evidences a role for AKT-mTOR pathway

Edoardo Missiaglia, Irene Dalai, Stefano Barbi, Stefania Beghelli, Massimo Falconi, Marco Della Peruta, Lorenzo Piemonti, Gabriele Capurso, Alessia Di Florio, Gianfranco Delle Fave, Paolo Pederzoli, Carlo M. Croce, Aldo Scarpa

Research output: Contribution to journalArticle

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Abstract

Purpose: We investigated the global gene expression in a large panel of pancreatic endocrine tumors (PETs) aimed at identifying new potential targets for therapy and biomarkers to predict patient outcome. Patients and Methods: Using a custom microarray, we analyzed 72 primary PETs, seven matched metastases, and 10 normal pancreatic samples. Relevant differentially expressed genes were validated by either quantitative real-time polymerase chain reaction or immunohistochemistry on tissue microarrays. Results: Our data showed that: tuberous sclerosis 2 (TSC2) and phosphatase and tensin homolog (PTEN) were downregulated in most of the primary tumors, and their low expression was significantly associated with shorter disease-free and overall survival; somatostatin receptor 2 (SSTR2) was absent or very low in insulinomas compared with nonfunctioning tumors; and expression of fibroblast growth factor 13 (FGF13) gene was significantly associated with the occurrence of liver metastasis and shorter disease-free survival. TSC2 and PTEN are two key inhibitors of the Akt/mammalian target of rapamycin (mTOR) pathway and the specific inhibition of mTOR with rapamycin or RAD001 inhibited cell proliferation of PET cell lines. Conclusion: Our results strongly support a role for PI3K/Akt/mTOR pathway in PET, which ties in with the fact that mTOR inhibitors have reached phase III trials in neuroendocrine tumors. The finding of differential SSTR expression raises the potential for SSTR expression to be evaluated as a marker of response to somatostatin analogs. Finally, we identified FGF13 as a new prognostic marker that predicted poorer outcome in patients who were clinically considered free from disease.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalJournal of Clinical Oncology
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 10 2010

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Sirolimus
Neoplasms
Phosphoric Monoester Hydrolases
Disease-Free Survival
Neoplasm Metastasis
Insulinoma
Endocrine Cells
Neuroendocrine Tumors
Somatostatin
Tumor Cell Line
Phosphatidylinositol 3-Kinases
Genes
Real-Time Polymerase Chain Reaction
Down-Regulation
Biomarkers
Immunohistochemistry
Cell Proliferation
Gene Expression
Liver
fibroblast growth factor 13

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Missiaglia, E., Dalai, I., Barbi, S., Beghelli, S., Falconi, M., Della Peruta, M., ... Scarpa, A. (2010). Pancreatic endocrine tumors: Expression profiling evidences a role for AKT-mTOR pathway. Journal of Clinical Oncology, 28(2), 245-255. https://doi.org/10.1200/JCO.2008.21.5988

Pancreatic endocrine tumors : Expression profiling evidences a role for AKT-mTOR pathway. / Missiaglia, Edoardo; Dalai, Irene; Barbi, Stefano; Beghelli, Stefania; Falconi, Massimo; Della Peruta, Marco; Piemonti, Lorenzo; Capurso, Gabriele; Di Florio, Alessia; Delle Fave, Gianfranco; Pederzoli, Paolo; Croce, Carlo M.; Scarpa, Aldo.

In: Journal of Clinical Oncology, Vol. 28, No. 2, 10.01.2010, p. 245-255.

Research output: Contribution to journalArticle

Missiaglia, E, Dalai, I, Barbi, S, Beghelli, S, Falconi, M, Della Peruta, M, Piemonti, L, Capurso, G, Di Florio, A, Delle Fave, G, Pederzoli, P, Croce, CM & Scarpa, A 2010, 'Pancreatic endocrine tumors: Expression profiling evidences a role for AKT-mTOR pathway', Journal of Clinical Oncology, vol. 28, no. 2, pp. 245-255. https://doi.org/10.1200/JCO.2008.21.5988
Missiaglia, Edoardo ; Dalai, Irene ; Barbi, Stefano ; Beghelli, Stefania ; Falconi, Massimo ; Della Peruta, Marco ; Piemonti, Lorenzo ; Capurso, Gabriele ; Di Florio, Alessia ; Delle Fave, Gianfranco ; Pederzoli, Paolo ; Croce, Carlo M. ; Scarpa, Aldo. / Pancreatic endocrine tumors : Expression profiling evidences a role for AKT-mTOR pathway. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 2. pp. 245-255.
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AU - Falconi, Massimo

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AU - Piemonti, Lorenzo

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