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Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma

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Abstract

Purpose

Constitutive activation of JAK/STAT pathway is observed in various solid tumors and hematological malignancies. SOCS3 acts as a key negative regulator of JAK/STAT pathway and represents one of the candidate tumor suppressor genes. In the current study, we aimed to evaluate SOCS3 expression in breast carcinoma and to explore the prognostic significance of SOCS3.

Methods

The expression of SOCS3 was measured by Western blot and immunohistochemistry in breast carcinoma cells and a large cohort of tissue microarray, respectively.

Results

Among 367 human primary breast tumors, SOCS3 protein was detected in 103 patients. Deficient SOCS3 expression correlated significantly with lymph node metastasis (P = 0.003), blood vessel invasion (P = 0.029), VEGF (P = 0.001) and Ki-67 (P = 0.027). Univariate and multivariate analyses revealed that SOCS3 expression was an independent prognostic factor for disease-free survival (P < 0.0001). A positive SOCS3 protein expression correlated significantly with a low pSTAT3 protein expression in breast carcinoma (P = 0.015). The patients with a SOCS3 (+)/pSTAT3 (−) phenotype had a better prognosis than any other combination (DFI: P < 0.0001, BCSS: P = 0.013).

Conclusions

Deficient expression of SOCS3 is associated with an aggressive phenotype and portends a poor clinical outcome in breast carcinoma.

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Abbreviations

ANT:

Adjacent non-cancerous tissues

BCSS:

Breast carcinoma-specific survival

CI:

Confidence interval

DFI:

Disease-free interval

ER:

Estrogen receptor

IDC:

Infiltrating ductal carcinoma

IHC:

Immunohistochemistry

LN:

Lymph node

PR:

Progesterone receptor

RR:

Relative risk

SOCS3:

Suppressor of cytokine signaling 3

STAT3:

Signal transducers and activators of transcription 3

TSG:

Tumor suppressor gene

TMA:

Tissue microarray

SDS:

Sodium dodecyl sulfate

VEGF:

Vascular endothelial growth factor

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Conflict of interest statement

The author(s) indicated no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Oncology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai, 200433, People’s Republic of China

    Mingzhen Ying, Linjun Yang, Mei Wang, Ning Wang & Yajie Wang

  2. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People’s Republic of China

    Dawei Li

  3. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Ying Chen & Miaoxia He

Authors
  1. Mingzhen Ying
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  2. Dawei Li
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  3. Linjun Yang
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  4. Mei Wang
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  5. Ning Wang
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  6. Ying Chen
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  7. Miaoxia He
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  8. Yajie Wang
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Correspondence to Yajie Wang.

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Ying, M., Li, D., Yang, L. et al. Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma. J Cancer Res Clin Oncol 136, 1617–1626 (2010). https://doi.org/10.1007/s00432-010-0819-6

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  • DOI: https://doi.org/10.1007/s00432-010-0819-6

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