TY - JOUR
T1 - Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.
AU - Malinowsky, K.
AU - Nitsche, U.
AU - Janssen, K. P.
AU - Bader, F. G.
AU - Späth, C.
AU - Drecoll, E.
AU - Keller, G.
AU - Höfler, H.
AU - Slotta-Huspenina, J.
AU - Becker, K. F.
N1 - Funding Information:
This study received funding from the German Federal Ministry of Education and Research (BMBF) Leading-Edge Cluster m4 Personalised Medicine and Targeted Therapies, grant no. 01EX1020D. We would like to thank Christina Schott, Christian Beese Ruth Wichnalek and Susanne Plaschke for excellent technical support. Anna Munzig contributed to the analysis of MSI and Johanna Donhauser contributed to the analysis of BRAF and KRAS mutational status.
PY - 2014/4/15
Y1 - 2014/4/15
N2 - Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel. Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis. Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.
AB - Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel. Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis. Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.
UR - http://www.scopus.com/inward/record.url?scp=84901849101&partnerID=8YFLogxK
U2 - 10.1038/bjc.2014.100
DO - 10.1038/bjc.2014.100
M3 - Article
C2 - 24619078
AN - SCOPUS:84901849101
SN - 0007-0920
VL - 110
SP - 2081
EP - 2089
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -