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 language | English |
|---|---|
| Pages (from-to) | 245-255 |
| Number of pages | 11 |
| Journal | Journal of Clinical Oncology |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 10 2010 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
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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 journal › Article
}
TY - JOUR
T1 - Pancreatic endocrine tumors
T2 - Expression profiling evidences a role for AKT-mTOR pathway
AU - Missiaglia, Edoardo
AU - Dalai, Irene
AU - Barbi, Stefano
AU - Beghelli, Stefania
AU - Falconi, Massimo
AU - Della Peruta, Marco
AU - Piemonti, Lorenzo
AU - Capurso, Gabriele
AU - Di Florio, Alessia
AU - Delle Fave, Gianfranco
AU - Pederzoli, Paolo
AU - Croce, Carlo M.
AU - Scarpa, Aldo
PY - 2010/1/10
Y1 - 2010/1/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=74949122343&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74949122343&partnerID=8YFLogxK
U2 - 10.1200/JCO.2008.21.5988
DO - 10.1200/JCO.2008.21.5988
M3 - Article
C2 - 19917848
AN - SCOPUS:74949122343
VL - 28
SP - 245
EP - 255
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 2
ER -