| Title |
Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability
|
|---|---|
| Published in |
Breast Cancer Research, April 2018
|
| DOI | 10.1186/s13058-018-0953-7 |
| Pubmed ID | |
| Authors |
Wen-Shan Liu, Shih-Hsuan Chan, Hong-Tai Chang, Guan-Cheng Li, Ya-Ting Tu, Hui-Hwa Tseng, Ting-Ying Fu, Hui-Yu Chang, Huei-Han Liou, Luo-Ping Ger, Kuo-Wang Tsai |
| Abstract |
The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer. Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cancer. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 18% |
| Researcher | 4 | 10% |
| Student > Bachelor | 4 | 10% |
| Librarian | 3 | 8% |
| Student > Master | 3 | 8% |
| Other | 8 | 21% |
| Unknown | 10 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 28% |
| Medicine and Dentistry | 6 | 15% |
| Engineering | 2 | 5% |
| Agricultural and Biological Sciences | 2 | 5% |
| Immunology and Microbiology | 1 | 3% |
| Other | 6 | 15% |
| Unknown | 11 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 April 2018.
All research outputs
#19,951,180
of 25,382,440 outputs
Outputs from Breast Cancer Research
#1,657
of 2,054 outputs
Outputs of similar age
#238,331
of 324,262 outputs
Outputs of similar age from Breast Cancer Research
#16
of 22 outputs
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