Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab

E. Zulato, F. Bergamo, A. De Paoli, G. Griguolo, G. Esposito, G. L. De Salvo, C. Mescoli, M. Rugge, M. Nardin, L. Di Grazia, S. Lonardi, S. Indraccolo, V. Zagonel

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background:AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.Methods:Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.Results:Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).Conclusions:Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalBritish Journal of Cancer
Volume111
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

AMP-Activated Protein Kinases
Colorectal Neoplasms
Drug Therapy
Vascular Endothelial Growth Factor A
Survival
Bevacizumab
Neoplasms
Phosphotransferases
Biomarkers
Immunohistochemistry

Keywords

  • AMPK
  • angiogenesis
  • bevacizumab
  • biomarker
  • colorectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab. / Zulato, E.; Bergamo, F.; De Paoli, A.; Griguolo, G.; Esposito, G.; De Salvo, G. L.; Mescoli, C.; Rugge, M.; Nardin, M.; Di Grazia, L.; Lonardi, S.; Indraccolo, S.; Zagonel, V.

In: British Journal of Cancer, Vol. 111, No. 1, 2014, p. 25-32.

Research output: Contribution to journalArticle

@article{c6ab278c2bfb4c10bafb46e654ac2d97,
title = "Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab",
abstract = "Background:AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.Methods:Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.Results:Fourteen patients (29.2{\%}) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8{\%}) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).Conclusions:Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.",
keywords = "AMPK, angiogenesis, bevacizumab, biomarker, colorectal cancer",
author = "E. Zulato and F. Bergamo and {De Paoli}, A. and G. Griguolo and G. Esposito and {De Salvo}, {G. L.} and C. Mescoli and M. Rugge and M. Nardin and {Di Grazia}, L. and S. Lonardi and S. Indraccolo and V. Zagonel",
year = "2014",
doi = "10.1038/bjc.2014.274",
language = "English",
volume = "111",
pages = "25--32",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab

AU - Zulato, E.

AU - Bergamo, F.

AU - De Paoli, A.

AU - Griguolo, G.

AU - Esposito, G.

AU - De Salvo, G. L.

AU - Mescoli, C.

AU - Rugge, M.

AU - Nardin, M.

AU - Di Grazia, L.

AU - Lonardi, S.

AU - Indraccolo, S.

AU - Zagonel, V.

PY - 2014

Y1 - 2014

N2 - Background:AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.Methods:Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.Results:Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).Conclusions:Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.

AB - Background:AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.Methods:Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.Results:Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).Conclusions:Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.

KW - AMPK

KW - angiogenesis

KW - bevacizumab

KW - biomarker

KW - colorectal cancer

UR - http://www.scopus.com/inward/record.url?scp=84904094903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904094903&partnerID=8YFLogxK

U2 - 10.1038/bjc.2014.274

DO - 10.1038/bjc.2014.274

M3 - Article

C2 - 24892446

AN - SCOPUS:84904094903

VL - 111

SP - 25

EP - 32

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -