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Increased pSmad2 expression and cytoplasmic predominant presence of TGF-βRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study

  • Epidemiology
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Abstract

Perturbations of transforming growth factor-beta (TGF-β) signaling are pivotal to tumorigenesis and tumor progression through their effects on cell proliferation and cell invasion. This study aims to evaluate the association of TGF-βRII and pSmad2 protein expressions in breast tissue with clinicopathological factors and prognosis of breast cancer. Expression of the TGF-βRII and pSmad2 proteins was assessed in breast tissue of 1,045 breast cancer cases in the Shanghai Breast Cancer Study using a double immunofluorescence staining method, which was validated with standard single immunostains. TGF-βRII expression intensity was positively associated with younger age at diagnosis (P = 0.03), pre-menopausal status (P = 0.03), and lower TNM stage (P = 0.04). Cytoplasmic predominant expression pattern of TGF-βRII was associated with older age at diagnosis (P = 0.04) and invasive histological type (P = 0.03). Increased pSmad2 expression was associated with higher breast cancer grade (P < 0.01). Higher pSmad2 expression [HR (95 % CI):1.48 (1.07–2.04), P = 0.02] and cytoplasmic predominant TGF-βRII expression [HR (95 % CI): 1.80 (1.08–3.00), P = 0.02] were significantly associated with reduced cancer-free survival. Our data suggest that TGF-βRII and pSmad2 expressions are associated with certain clinical and pathologic features of breast cancer. A cytoplasmic predominant TGF-βRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival. Our study provides additional evidence to support the important role of TGF-β signaling in breast cancer prognosis.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

DFS:

Disease-free survival

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

PR:

Progesterone receptor

pSmad2:

Phosphorylated Smad2

SBCS:

Shanghai Breast Cancer Study

TGF-β:

Transforming growth factor-beta

TGF-βRI:

Transforming growth factor-beta receptor I

TGF-βRII:

Transforming growth factor-beta receptor II

TMA:

Tissue microarray

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Acknowledgments

The authors thank study participants and research staff for their contributions and commitment to this project. We thank Regina Courtney for technical assistance and Jacqueline Stern for assistance with editing and manuscript preparation. The immunofluorescence staining was performed at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485). This research was supported by research grants from the National Institutes of health (R01CA064277, R01CA090899, R01CA118229, and R01CA122756).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All data collection was conducted with approval of appropriate institutional review boards to protect human subjects with consent and data protection systems in place. Data analysis for this manuscript was conducted on de-identified data sets.

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Author notes

  1. Shenghui Wu

    Present address: Department of Epidemiology & Biostatistics, University of Texas Health Science Center at San Antonio-Laredo Campus, Laredo, TX, 78041, USA

Authors and Affiliations

  1. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN, 37232, USA

    Qingchao Qiu, Yinghao Su, Hui Cai, Shenghui Wu, Wei Zheng, Xiao Ou Shu & Qiuyin Cai

  2. Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

    Ying Zheng & Wei Lu

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  1. Qingchao Qiu
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Correspondence to Qiuyin Cai.

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Qiu, Q., Su, Y., Zheng, Y. et al. Increased pSmad2 expression and cytoplasmic predominant presence of TGF-βRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study. Breast Cancer Res Treat 149, 467–477 (2015). https://doi.org/10.1007/s10549-014-3251-9

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  • DOI: https://doi.org/10.1007/s10549-014-3251-9

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