Favorable prognostic value of SOCS2 and IGF-I in breast cancer
Open Access
- 25 July 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 7 (1), 136-9
- https://doi.org/10.1186/1471-2407-7-136
Abstract
Background Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. Methods We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. Results SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002). Conclusion This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors.Keywords
This publication has 49 references indexed in Scilit:
- Expression patterns of insulin-like growth factor 1 (IGF-I) and its receptor in mammary tissues and their associations with breast cancer survivalBreast Cancer Research and Treatment, 2006
- Suppressor of cytokine signalling 2 (SOCS-2) expression in breast carcinomaJournal of Clinical Pathology, 2005
- Epigenetic inactivation of SOCS‐1 by CpG island hypermethylation in human gastric carcinomaInternational Journal of Cancer, 2004
- Insulin-like growth factors and neoplasiaNature Reviews Cancer, 2004
- A Gene-Expression Signature as a Predictor of Survival in Breast CancerThe New England Journal of Medicine, 2002
- SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2Online Journal of Public Health Informatics, 2002
- Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesisOncogene, 2000
- Circulating concentrations of insulin-like growth factor I and risk of breast cancerThe Lancet, 1998
- Cloning and Characterization of Novel CIS Family GenesBiochemical and Biophysical Research Communications, 1997
- Prognosis in Stage II “T1N1M0”Breast CancerAnnals of Surgery, 1981