NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis
Abstract Background A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the g...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-019-1236-7 |
| _version_ | 1818672382500405248 |
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| author | Lingfeng Wan Tao Liu Zhipeng Hong You Pan Steven T. Sizemore Junran Zhang Zhefu Ma |
| author_facet | Lingfeng Wan Tao Liu Zhipeng Hong You Pan Steven T. Sizemore Junran Zhang Zhefu Ma |
| author_sort | Lingfeng Wan |
| collection | DOAJ |
| description | Abstract Background A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4. Methods The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan–Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method. Results NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively). Conclusions NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment. |
| first_indexed | 2024-12-17T07:39:01Z |
| format | Article |
| id | doaj.art-880b184b42044c0886ed6f0b5e9ed0af |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-17T07:39:01Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-880b184b42044c0886ed6f0b5e9ed0af2022-12-21T21:58:14ZengBMCBreast Cancer Research1465-542X2019-12-0121111610.1186/s13058-019-1236-7NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosisLingfeng Wan0Tao Liu1Zhipeng Hong2You Pan3Steven T. Sizemore4Junran Zhang5Zhefu Ma6Department of Breast Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Breast Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Radiation Oncology, The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research InstituteDepartment of Breast Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Radiation Oncology, The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research InstituteDepartment of Radiation Oncology, The Ohio State University, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research InstituteDepartment of Breast Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract Background A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4. Methods The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan–Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method. Results NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively). Conclusions NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.https://doi.org/10.1186/s13058-019-1236-7Breast cancerNEDD4PrognosisTumor progression |
| spellingShingle | Lingfeng Wan Tao Liu Zhipeng Hong You Pan Steven T. Sizemore Junran Zhang Zhefu Ma NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis Breast Cancer Research Breast cancer NEDD4 Prognosis Tumor progression |
| title | NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| title_full | NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| title_fullStr | NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| title_full_unstemmed | NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| title_short | NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| title_sort | nedd4 expression is associated with breast cancer progression and is predictive of a poor prognosis |
| topic | Breast cancer NEDD4 Prognosis Tumor progression |
| url | https://doi.org/10.1186/s13058-019-1236-7 |
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