J Breast Cancer.  2020 Feb;23(1):36-46. 10.4048/jbc.2020.23.e12.

Downregulation of N-myc and STAT Interactor Protein Predicts Aggressive Tumor Behavior and Poor Prognosis in Invasive Ductal Carcinoma

• Choi JE
• Hyun CL
• Jin MS
• Lee KM
• Moon JH
• Ryu HS

• KMID: 2470880
• DOI: http://doi.org/10.4048/jbc.2020.23.e12

Abstract

PURPOSE
We investigated the expression of the N-myc and STAT interactor (NMI) protein in invasive ductal carcinoma tissue and estimated its clinicopathologic significance as a prognostic factor. The expression levels and prognostic significance of NMI were also analyzed according to the molecular subgroup of breast cancers.
METHODS
Human NMI detection by immunohistochemistry was performed using tissue microarrays of 382 invasive ductal carcinomas. The correlation of NMI expression with patient clinicopathological parameters and prognostic significance was analyzed and further assessed according to the molecular subgroup of breast cancers. Moreover, in vitro experiments with 13 breast cancer cell lines were carried out. We also validated NMI expression significance in The Cancer Genome Atlas cohort using the Human Protein Atlas (HPA) database.
RESULTS
Low NMI expression was observed in 190 cases (49.7%). Low NMI expression was significantly associated with the "triple-negative" molecular subtype (p < 0.001), high nuclear grade (p < 0.001), high histologic grade (p < 0.001), and advanced anatomic stage (p = 0.041). Patients with low NMI expression had poorer progression-free survival (p = 0.038) than patients with high NMI expression. Low NMI expression was not significantly associated with patient prognosis in the molecular subgroup analysis. In vitro, a reduction of NMI expression was observed in 8 breast cancer cell lines, especially in the estrogen receptor-positive and basal B type of triple-negative breast cancer molecular subgroups. The HPA database showed that low NMI expression levels were associated with a lower survival probability compared with that associated with high NMI expression (p = 0.053).
CONCLUSION
NMI expression could be a useful prognostic biomarker and a potential novel therapeutic target in invasive ductal carcinoma.

Keyword

Biomarkers, tumor; Breast neoplasms; Databases, genetic; NMI protein, human

MeSH Terms

Biomarkers, Tumor
Breast
Breast Neoplasms
Carcinoma, Ductal*
Cell Line
Cohort Studies
Databases, Genetic
Disease-Free Survival
Down-Regulation*
Estrogens
Genome
Humans
Immunohistochemistry
In Vitro Techniques
Prognosis*
Triple Negative Breast Neoplasms
Biomarkers, Tumor
Estrogens

Figure

• 

  Figure 1 Representative immunohistochemical results for NMI expression in normal breast tissue and breast cancer. (A) NMI expression is observed in the cytoplasm of normal breast epithelial cells (IHC for NMI, 400× magnification). (B, C) Loss of NMI expression and presence of NMI expression in breast cancers (IHC for NMI, 4× and 400× (inlet) magnification, respectively).NMI = N-myc and STAT interactor; IHC = immunohistochemistry.

• 

  Figure 2 Kaplan-Meier survival analyses for the NMI expression as a determinant of PFS.NMI = N-myc and STAT interactor; PFS = progression-free survival.

• 

  Figure 3 NMI expression and patient PFS analysis according to each molecular subtype. (A) Luminal A; (B) Lumina B; (C) HER2 positive; (D) Triple-negative breast cancer.NMI = N-myc and STAT interactor; PFS = progression-free survival; HER2 = human epidermal growth factor 2.

• 

  Figure 4 (A) Western blot analysis shows that NMI expression is reduced in some of the breast cancer cell lines. (B) Subgroup analyses of NMI expression levels in breast cancer cell lines.NMI = N-myc and STAT interactor; HER2 = human epidermal growth factor 2; ER = estrogen receptor; RPKM = reads per kilobase of transcript per million mapped reads; TNBC = triple-negative breast cancer.

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