Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 8, Pages 2081-2089Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.100
Keywords
colon cancer; biomarker; reverse-phase protein array; PI3K; AKT; prognosis; survival
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Funding
- German Federal Ministry of Education and Research (BMBF) Leading-Edge Cluster m4 Personalised Medicine and Targeted Therapies [01EX1020D]
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Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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