IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients
1 Department of Biomedicine, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland
2 Division of Medical Oncology, Department of Internal Medicine, St Claraspital, Kleinriehenstrasse 20, CH-4016 Basel, Switzerland
3 Division of Medical Oncology, Department of Internal Medicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
4 Department of Gynecology and Obstetrics, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
BMC Medicine 2010, 8:1 doi:10.1186/1741-7015-8-1Published: 5 January 2010
Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.
We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies.
Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset).
Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.