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NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer

1
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3711; https://doi.org/10.3390/cancers12123711
Received: 3 November 2020 / Revised: 4 December 2020 / Accepted: 8 December 2020 / Published: 10 December 2020
(This article belongs to the Section Cancer Biomarkers)
Inflammatory breast cancer (IBC) is a rare and aggressive variant of breast cancer that is responsible for a significant number of breast cancer-related deaths. Herein, we describe how the expression of a specific protein named N-myc downstream-regulated gene 1 (NDRG1), commonly described as a gene that prevents the spread of cancer cells to distant organs, may have a paradoxical role in cancer progression in IBC. We found that the level of expression of NDRG1 in tumor tissues predicts the survival outcome of patients with IBC. We also observed that NDRG1, together with other important prognostic factors such as estrogen receptor status and stage, could be used to further analyze prognostic outcome or treatment response of patients.
NDRG1 is widely described as a metastasis suppressor in breast cancer. However, we found that NDRG1 is critical in promoting tumorigenesis and brain metastasis in mouse models of inflammatory breast cancer (IBC), a rare but highly aggressive form of breast cancer. We hypothesized that NDRG1 is a prognostic marker associated with poor outcome in patients with IBC. NDRG1 levels in tissue microarrays from 64 IBC patients were evaluated by immunohistochemical staining with NDRG1 (32 NDRG1-low (≤median), 32 NDRG1-high (>median)). Overall and disease-free survival (OS and DSS) were analyzed with Kaplan–Meier curves and log-rank test. Univariate analysis showed NDRG1 expression, tumor grade, disease stage, estrogen receptor (ER) status, and receipt of adjuvant radiation to be associated with OS and DSS. NDRG1-high patients had poorer 10-year OS and DSS than NDRG1-low patients (OS, 19% vs. 45%, p = 0.0278; DSS, 22% vs. 52%, p = 0.0139). On multivariable analysis, NDRG1 independently predicted OS (hazard ratio (HR) = 2.034, p = 0.0274) and DSS (HR = 2.287, p = 0.0174). NDRG1-high ER-negative tumors had worse outcomes OS, p = 0.0003; DSS, p = 0.0003; and NDRG1-high tumors that received adjuvant radiation treatment had poor outcomes (OS, p = 0.0088; DSS, p = 0.0093). NDRG1 was a significant independent prognostic factor for OS and DSS in IBC patients. Targeting NDRG1 may represent a novel strategy for improving clinical outcomes for patients with IBC. View Full-Text
Keywords: NDRG1; N-myc downstream-regulated gene 1; IBC; inflammatory breast cancer; survival NDRG1; N-myc downstream-regulated gene 1; IBC; inflammatory breast cancer; survival
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MDPI and ACS Style

Villodre, E.S.; Gong, Y.; Hu, X.; Huo, L.; Yoon, E.C.; Ueno, N.T.; Woodward, W.A.; Tripathy, D.; Song, J.; Debeb, B.G. NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer. Cancers 2020, 12, 3711. https://doi.org/10.3390/cancers12123711

AMA Style

Villodre ES, Gong Y, Hu X, Huo L, Yoon EC, Ueno NT, Woodward WA, Tripathy D, Song J, Debeb BG. NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer. Cancers. 2020; 12(12):3711. https://doi.org/10.3390/cancers12123711

Chicago/Turabian Style

Villodre, Emilly S.; Gong, Yun; Hu, Xiaoding; Huo, Lei; Yoon, Esther C.; Ueno, Naoto T.; Woodward, Wendy A.; Tripathy, Debu; Song, Juhee; Debeb, Bisrat G. 2020. "NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer" Cancers 12, no. 12: 3711. https://doi.org/10.3390/cancers12123711

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