التفاصيل البيبلوغرافية
| العنوان: |
A CTC-Cluster-Specific Signature Derived from OMICS Analysis of Patient-Derived Xenograft Tumors Predicts Outcomes in Basal-Like Breast Cancer |
| المؤلفون: |
Hariprasad Thangavel, Carmine De Angelis, Suhas Vasaikar, Raksha Bhat, Mohit Kumar Jolly, Chandandeep Nagi, Chad J. Creighton, Fengju Chen, Lacey E. Dobrolecki, Jason T. George, Tanya Kumar, Noor Mazin Abdulkareem, Sufeng Mao, Agostina Nardone, Mothaffar Rimawi, C. Kent Osborne, Michael T. Lewis, Herbert Levine, Bing Zhang, Rachel Schiff, Mario Giuliano, Meghana V. Trivedi |
| المصدر: |
Journal of Clinical Medicine; Volume 8; Issue 11; Pages: 1772 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2019 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
circulating tumor cells, CTC clusters, triple-negative breast cancer, patient-derived xenograft, RPPA, transcriptomics, B-cell lymphoma 2, apoptosis |
| الوصف: |
Circulating tumor cell clusters (CTCcl) have a higher metastatic potential compared to single CTCs and predict long-term outcomes in breast cancer (BC) patients. Because of the rarity of CTCcls, molecular characterization of primary tumors that give rise to CTCcl hold significant promise for better diagnosis and target discovery to combat metastatic BC. In our study, we utilized the reverse-phase protein array (RPPA) and transcriptomic (RNA-Seq) data of 10 triple-negative BC patient-derived xenograft (TNBC PDX) transplantable models with CTCs and evaluated expression of upregulated candidate protein Bcl2 (B-cell lymphoma 2) by immunohistochemistry (IHC). The sample-set consisted of six CTCcl-negative (CTCcl−) and four CTCcl-positive (CTCcl+) models. We analyzed the RPPA and transcriptomic profiles of CTCcl− and CTCcl+ TNBC PDX models. In addition, we derived a CTCcl-specific gene signature for testing if it predicted outcomes using a publicly available dataset from 360 patients with basal-like BC. The RPPA analysis of CTCcl+ vs. CTCcl− TNBC PDX tumors revealed elevated expression of Bcl2 (false discovery rate (FDR) < 0.0001, fold change (FC) = 3.5) and reduced acetyl coenzyme A carboxylase-1 (ACC1) (FDR = 0.0005, FC = 0.3) in CTCcl+ compared to CTCcl− tumors. Genome-wide transcriptomic analysis of CTCcl+ vs. CTCcl− tumors revealed 549 differentially expressed genes associated with the presence of CTCcls. Apoptosis was one of the significantly downregulated pathways (normalized enrichment score (NES) = −1.69; FDR < 0.05) in TNBC PDX tumors associated with CTCcl positivity. Two out of four CTCcl+ TNBC PDX primary tumors had high Bcl2 expression by IHC (H-score > 34); whereas, only one of six CTCcl− TNBC PDX primary tumors met this criterion. Evaluation of epithelial-mesenchymal transition (EMT)-specific signature did not show significant differences between CTCcl+ and CTCcl− tumors. However, a gene signature associated with the presence of CTCcls in TNBC PDX models was associated with worse relapse-free ... |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Oncology; https://dx.doi.org/10.3390/jcm8111772Test |
| DOI: |
10.3390/jcm8111772 |
| الإتاحة: |
https://doi.org/10.3390/jcm8111772Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.1B6190A7 |
| قاعدة البيانات: |
BASE |
