HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Mouse Model
2.1.1. Heterogeneous HER2 Expression Is Associated with Short Survival in Metastatic Breast Cancer
2.1.2. HER2-60 Brain Metastasis Showed Low Expression of Caspase-1 on RNA Sequence Analysis
2.2. Clinical Study
3. Discussion
4. Materials and Methods
4.1. Basic Study
4.1.1. Cell Culture and Establishment of HER2-60 and HER2-90 Cell Lines
4.1.2. Brain Metastasis Model
4.1.3. Bioluminescence Imaging
4.1.4. Selecting Samples for RNA Sequence Analysis
4.1.5. RNA Sequence
4.1.6. Real Time RT-PCR
4.2. Clinical Study
4.2.1. Definition of HER2 Genetic Heterogeneity
4.2.2. Classification of HER2-positive Breast Cancer with or without HER2 Heterogeneity by IHC Staining
4.3. Survival Analysis
4.4. Ethics Statement
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
HER2 | human epidermal growth factor receptor 2 |
CEP17 | centromere on chromosome 17 |
NLRs | nucleotide oligomerization domain (NOD)-like receptors |
AIM2 | absent in melanoma |
NLRP3 | NLR family pyrin domain-containing protein 3 |
NLRC4 | NLR family caspase activation and recruitment domain (CARD) domain-containing protein 4 |
PYCARD | apoptosis-associated speck-like protein containing a CARD |
IHC | immunohistochemistry |
DFS | disease free survival |
ASCO/CAP | American society of clinical oncology and College of American pathologist |
OS | overall survival |
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Gene Symbol | 231-Luc No. 1 | 231-Luc No. 2 | HER2-60 | HER2-90 |
---|---|---|---|---|
CASP1 | 2.83 | 0 | 0 | 21.07 |
AIM2 | 11.62 | 2.96 | 7.80 | 26.59 |
NLRP3 | 5.65 | 4.51 | 6.67 | 6.10 |
NLRC4 | 0.61 | 0 | 0 | 1.49 |
PYCARD | 7.59 | 0 | 7.56 | 19.61 |
IL1B | 4.85 | 1.28 | 0.95 | 3.06 |
IL18 | 45.61 | 49.12 | 23.71 | 20.75 |
Primer | Forward | Reverse |
---|---|---|
mouse Gapdh | 5-ACTAACATCAAATGGGGTGAGGCC-3 | 5-GGATGCATTGCTGACAATCTTGAGTGA-3 |
human GAPDH | 5-CAAAATCAAGTGGGGCGATGCTGGC-3 | 5-GGCATTGCTGATGATCTTGAGGCT-3 |
CASP1 | 5-TCCCTAGAAGAAGCTCAAAGGATATG-3 | 5-CGTGTGCGGCTTGACTTG-3 |
AIM2 | 5-CAGAAATGATGTCGCAAAGCA-3 | 5-TCAGTACCATAACTGGCAAACAG-3 |
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Share and Cite
Hosonaga, M.; Arima, Y.; Sampetrean, O.; Komura, D.; Koya, I.; Sasaki, T.; Sato, E.; Okano, H.; Kudoh, J.; Ishikawa, S.; et al. HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer. Int. J. Mol. Sci. 2018, 19, 2158. https://doi.org/10.3390/ijms19082158
Hosonaga M, Arima Y, Sampetrean O, Komura D, Koya I, Sasaki T, Sato E, Okano H, Kudoh J, Ishikawa S, et al. HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer. International Journal of Molecular Sciences. 2018; 19(8):2158. https://doi.org/10.3390/ijms19082158
Chicago/Turabian StyleHosonaga, Mari, Yoshimi Arima, Oltea Sampetrean, Daisuke Komura, Ikuko Koya, Takashi Sasaki, Eiichi Sato, Hideyuki Okano, Jun Kudoh, Shumpei Ishikawa, and et al. 2018. "HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer" International Journal of Molecular Sciences 19, no. 8: 2158. https://doi.org/10.3390/ijms19082158