| Title |
Prognostic and functional importance of the engraftment-associated genes in the patient-derived xenograft models of triple-negative breast cancers
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, October 2015
|
| DOI | 10.1007/s10549-015-3585-y |
| Pubmed ID | |
| Authors |
Hyeong-Gon Moon, Keunhee Oh, Jiwoo Lee, Minju Lee, Ju-Yeon Kim, Tae-Kyung Yoo, Myung Won Seo, Ae Kyung Park, Han Suk Ryu, Eun-Jung Jung, Namshin Kim, Seongmun Jeong, Wonshik Han, Dong-Sup Lee, Dong-Young Noh |
| Abstract |
We aimed to identify the factors affecting the successful tumor engraftment in breast cancer patient-derived xenograft (PDX) models. Further, we investigated the prognostic significance and the functional importance of the PDX engraftment-related genes in triple-negative breast cancers (TNBC). The clinico-pathologic features of 81 breast cancer patients whose tissues were used for PDX transplantation were analyzed to identify the factors affecting the PDX engraftment. A gene signature associated with the PDX engraftment was discovered and its clinical importance was tested in a publicly available dataset and in vitro assays. Nineteen out of 81 (23.4 %) transplanted tumors were successfully engrafted into the PDX models. The engraftment rate was highest in TNBC when compared to other subtypes (p = 0.001) and in recurrent or chemotherapy-resistant tumors compared to newly diagnosed primary tumors (p = 0.024). PDX tumors originated from the TNBC cases showed more rapid tumor growth in mice. Gene expression profiling showed that down-regulation of genes involved in the tumor-immune interaction was significantly associated with the successful PDX engraftment. The engraftment gene signature was associated with worse survival outcome when tested in publicly available mRNA datasets of TNBC cases. Among the engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in triple-negative breast cancer cell lines, and siRNA-based gene silencing resulted in reduced cell invasion and proliferation in vitro. Our results show that the PDX engraftment may reflect the aggressive phenotype in breast cancer. Genes associated with the PDX engraftment may provide a novel prognostic biomarker and therapeutic targets in TNBC. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 33% |
| France | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Unknown | 40 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 17% |
| Researcher | 6 | 15% |
| Student > Doctoral Student | 3 | 7% |
| Professor > Associate Professor | 3 | 7% |
| Student > Bachelor | 3 | 7% |
| Other | 6 | 15% |
| Unknown | 13 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 32% |
| Biochemistry, Genetics and Molecular Biology | 10 | 24% |
| Agricultural and Biological Sciences | 4 | 10% |
| Unknown | 14 | 34% |
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 09 August 2016.
All research outputs
#15,348,067
of 22,829,683 outputs
Outputs from Breast Cancer Research and Treatment
#3,297
of 4,659 outputs
Outputs of similar age
#162,602
of 277,499 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#42
of 81 outputs
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