Robust identification of target genes and outliers in triple-negative breast cancer data.
Stat Methods Med Res
; 28(10-11): 3042-3056, 2019.
Article
en En
| MEDLINE
| ID: mdl-30146936
ABSTRACT
Correct classification of breast cancer subtypes is of high importance as it directly affects the therapeutic options. We focus on triple-negative breast cancer which has the worst prognosis among breast cancer types. Using cutting edge methods from the field of robust statistics, we analyze Breast Invasive Carcinoma transcriptomic data publicly available from The Cancer Genome Atlas data portal. Our analysis identifies statistical outliers that may correspond to misdiagnosed patients. Furthermore, it is illustrated that classical statistical methods may fail to identify outliers due to their heavy influence, prompting the need for robust statistics. Using robust sparse logistic regression we obtain 36 relevant genes, of which ca. 60% have been previously reported as biologically relevant to triple-negative breast cancer, reinforcing the validity of the method. The remaining 14 genes identified are new potential biomarkers for triple-negative breast cancer. Out of these, JAM3, SFT2D2, and PAPSS1 were previously associated to breast tumors or other types of cancer. The relevance of these genes is confirmed by the new DetectDeviatingCells outlier detection technique. A comparison of gene networks on the selected genes showed significant differences between triple-negative breast cancer and non-triple-negative breast cancer data. The individual role of FOXA1 in triple-negative breast cancer and non-triple-negative breast cancer, and the strong FOXA1-AGR2 connection in triple-negative breast cancer stand out. The goal of our paper is to contribute to the breast cancer/triple-negative breast cancer understanding and management. At the same time it demonstrates that robust regression and outlier detection constitute key strategies to cope with high-dimensional clinical data such as omics data.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama Triple Negativas
/
Modelos Genéticos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Stat Methods Med Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Bélgica