Academic Journal

A novel prognostic two-gene signature for triple negative breast cancer

التفاصيل البيبلوغرافية
العنوان: A novel prognostic two-gene signature for triple negative breast cancer
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
الوصف
DOI:10.1038/s41379-020-0563-7