Favorable Prognostic Value of SOCS2 and IGF-I in Breast Cancer

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2007 Jul 27

PMID 17651480

Citations 36

Authors

Michael C Haffner

Barbara Petridou

Jean Phillipe Peyrat

Francoise Revillion

Elisabeth Muller-Holzner

Gunter Daxenbichler

Christian Marth

Wolfgang Doppler

Affiliations

Soon will be listed here.

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.

Citing Articles

The Association between the JAK-STAT Pathway and Hypertension among Kenyan Women Diagnosed with Breast Cancer.

Gitau J, Kinyori G, Sayed S, Saleem M, Makokha F, Kirabo A bioRxiv. 2024; .

PMID: 38895458 PMC: 11185763. DOI: 10.1101/2024.06.07.597892.

CEBPA Restrains the Malignant Progression of Breast Cancer by Prompting the Transcription of SOCS2.

Wang J, Ji W, Huang A, Liu Z, Chen D Mol Biotechnol. 2024; .

PMID: 38775935 DOI: 10.1007/s12033-024-01189-4.

SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway.

Lv Y, Xie X, Zou G, Kong M, Yang J, Chen J Sci Rep. 2023; 13(1):21814.

PMID: 38071211 PMC: 10710468. DOI: 10.1038/s41598-023-48591-7.

Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands.

Linossi E, Li K, Veggiani G, Tan C, Dehkhoda F, Hockings C Nat Commun. 2021; 12(1):7032.

PMID: 34857742 PMC: 8640019. DOI: 10.1038/s41467-021-26983-5.

Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.

Sun M, Tang C, Liu J, Jiang W, Yu H, Dong F BMC Cancer. 2021; 21(1):696.

PMID: 34120621 PMC: 8201682. DOI: 10.1186/s12885-021-08434-y.

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