Gene Expression Profiling of Breast Cancer Brain Metastasis

被引:58
作者
Lee, Ji Yun [1 ]
Park, Kyunghee [2 ]
Lee, Eunjin [2 ]
Ahn, TaeJin [2 ]
Jung, Hae Hyun [3 ]
Lim, Sung Hee [1 ]
Hong, Mineui [4 ]
Do, In-Gu [4 ]
Cho, Eun Yoon [4 ]
Kim, Duk-Hwan [5 ]
Kim, Ji-Yeon [1 ]
Ahn, Jin Seok [1 ]
Im, Young-Hyuck [1 ,2 ]
Park, Yeon Hee [1 ,3 ]
机构
[1] Sungkyunkwan Univ, Div Hematol Oncol, Dept Med, Samsung Med Ctr,Sch Med, Seoul, South Korea
[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Genom Inst,Samsung Biol Res Inst, Seoul, South Korea
[3] Sungkyunkwan Univ, Sch Med, SAIHST, Dept Hlth Sci & Technol, Seoul, South Korea
[4] Sungkyunkwan Univ, Innovat Canc Med Inst, Ctr Compan Diagnost, Samsung Med Ctr,Sch Med, Seoul, South Korea
[5] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Dept Mol Cell Biol, Suwon, South Korea
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
REPORTING RECOMMENDATIONS; MATRIX METALLOPROTEINASES; MOLECULAR PORTRAITS; P53; PROGNOSIS; IDENTIFICATION; SUBTYPES; MUTATIONS; PATHWAY; CELLS;
D O I
10.1038/srep28623
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM. Five of these genes, CXCL12, MMP2, MMP11, VCAM1, and MME, which have previously been associated with tumor progression, angiogenesis, and metastasis, clearly discriminated between primary BC and BCBM. Notably, the five genes were significantly upregulated in primary BC compared to BCBM. Conversely, SOX2 and OLIG2 genes were upregulated in BCBM. These genes may participate in metastatic colonization but not in primary tumor development. Among patient-matched paired samples (n = 17), a PAM50 molecular subtype conversion was observed in eight cases (47.1%), with a trend toward unfavorable subtypes in patients with the distinct gene expression. Our findings, although not conclusive, reveal differentially expressed genes that might mediate the brain metastasis process.
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页数:10
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共 58 条
[1]   Management of brain metastases: the indispensable role of surgery [J].
Al-Shamy, George ;
Sawaya, Raymond .
JOURNAL OF NEURO-ONCOLOGY, 2009, 92 (03) :275-282
[2]   Characteristics of basal cytokeratin expression in breast cancer [J].
Alshareeda, Alaa T. ;
Soria, Daniele ;
Garibaldi, Jonathan M. ;
Rakha, Emad ;
Nolan, Christopher ;
Ellis, Ian O. ;
Green, Andrew R. .
BREAST CANCER RESEARCH AND TREATMENT, 2013, 139 (01) :23-37
[3]   Role of Sox2 in the development of the mouse neocortex [J].
Bani-Yaghoub, Mahmud ;
Tremblay, Roger G. ;
Lei, Joy X. ;
Zhang, Dongling ;
Zurakowski, Bogdan ;
Sandhu, Jagdeep K. ;
Smith, Brandon ;
Ribecco-Lutkiewicz, Maria ;
Kennedy, Jessica ;
Walker, P. Roy ;
Sikorska, Marianna .
DEVELOPMENTAL BIOLOGY, 2006, 295 (01) :52-66
[4]   Luminal-B breast cancer and novel therapeutic targets [J].
Ben Tran ;
Bedard, Philippe L. .
BREAST CANCER RESEARCH, 2011, 13 (06)
[5]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[6]   Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics [J].
Bollig-Fischer, Aliccia ;
Michelhaugh, Sharon K. ;
Wijesinghe, Priyanga ;
Dyson, Greg ;
Kruger, Adele ;
Palanisamy, Nallasivam ;
Choi, Lydia ;
Alosh, Baraa ;
Ali-Fehmi, Rouba ;
Mittal, Sandeep .
ONCOTARGET, 2015, 6 (16) :14614-14624
[7]   Genes that mediate breast cancer metastasis to the brain [J].
Bos, Paula D. ;
Zhang, Xiang H. -F. ;
Nadal, Cristina ;
Shu, Weiping ;
Gomis, Roger R. ;
Nguyen, Don X. ;
Minn, Andy J. ;
van de Vijver, Marc J. ;
Gerald, William L. ;
Foekens, John A. ;
Massague, Joan .
NATURE, 2009, 459 (7249) :1005-U137
[8]   Molecular Origins of Cancer Molecular Basis of Metastasis [J].
Chiang, Anne C. ;
Massague, Joan .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (26) :2814-2823
[9]   New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[10]   The Biology of Brain Metastasis Challenges for Therapy [J].
Fidler, Isaiah J. .
CANCER JOURNAL, 2015, 21 (04) :284-293