Academic Journal
A novel prognostic two-gene signature for triple negative breast cancer
العنوان: | A novel prognostic two-gene signature for triple negative breast cancer |
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المؤلفون: | Alsaleem, Mansour A, Ball, Graham, Toss, Michael S, Raafat, Sara, Aleskandarany, Mohammed, Joseph, Chitra, Ogden, Angela, Bhattarai, Shristi, Rida, Padmashree C G, Mongan, Nigel P., Khani, Francesca, Davis, Melissa, Elemento, Olivier, Aneja, Ritu, Ellis, Ian O, Green, Andrew, Rakha, Emad |
بيانات النشر: | Nature Publishing Group |
سنة النشر: | 2020 |
المجموعة: | University of Nottingham: Repository@Nottingham |
مصطلحات موضوعية: | triple negative breast cancer, TNBC, prognostic gene signature, ANN, ACSM4, SPDYC, NGS, Nottingham Breast Cancer Research Centre |
الوصف: | The absence of a robust risk stratification tool for triple negative breast cancer (TNBC) underlies imprecise and non-selective treatment of these patients with cytotoxic chemotherapy. This study aimed to interrogate transcriptomes of TNBC resected samples using next generation sequencing to identify novel biomarkers associated with disease outcomes. A subset of cases (n=112) from a large, well-characterized cohort of primary TNBC (n=333) were subjected to RNA-sequencing. Reads were aligned to the human reference genome (GRCH38.83) using the STAR aligner and gene expression quantified using HTSEQ. We identified genes associated with distant metastasis-free survival and breast cancer-specific survival by applying supervised artificial neural network analysis with gene selection to the RNA-sequencing data. The prognostic ability of these genes was validated using the Breast Cancer Gene-Expression Miner v4. 0 and Genotype 2 outcome datasets. Multivariate Cox regression analysis identified a prognostic gene signature that was independently associated with poor prognosis. Finally, we corroborated our results from the two-gene prognostic signature by their protein expression using immunohistochemistry. Artificial neural network identified two gene panels that strongly predicted distant metastasis-free survival and breast cancer-specific survival. Univariate Cox regression analysis of 21 genes common to both panels revealed that the expression level of eight genes was independently associated with poor prognosis (p |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
Relation: | https://nottingham-repository.worktribe.com/output/4325602; Modern Pathology; Volume 33; Pagination 2208–2220 |
DOI: | 10.1038/s41379-020-0563-7 |
الاتاحة: | https://doi.org/10.1038/s41379-020-0563-7 https://nottingham-repository.worktribe.com/file/4325602/1/Main%20Text https://nottingham-repository.worktribe.com/output/4325602 |
Rights: | openAccess |
رقم الانضمام: | edsbas.769AC863 |
قاعدة البيانات: | BASE |
DOI: | 10.1038/s41379-020-0563-7 |
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