PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement
Genre
Journal ArticleDate
2019-01-01Author
Bonin, SPracella, D
Barbazza, R
Dotti, I
Boffo, S
Stanta, G
Subject
AdultBiomarkers, Tumor
Breast Neoplasms
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Phosphatidylinositol 3-Kinases
Prognosis
Proto-Oncogene Proteins c-akt
Receptor, ErbB-2
Receptors, Estrogen
Receptors, Progesterone
Retrospective Studies
Survival Rate
Permanent link to this record
http://hdl.handle.net/20.500.12613/4586
Metadata
Show full item recordDOI
10.1155/2019/7832376Abstract
© 2019 S. Bonin et al. Lymph node metastatic involvement persists to be among the most important predictors of recurrence and survival in breast carcinoma (BC). This study is aimed at investigating possible gene expression differences in primary BC between patients with or without lymph node involvement at the time of diagnosis. In a retrospective study, we investigated the potential prognostic role of 9 candidate biomarkers at the mRNA level in a cohort of 305 breast cancer patients, 151 lymph node-negative (LN-) and 154 lymph node-positive (LN+) individuals. The analyzed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3CB, AKT1, AKT2, and AKT3), RB pathway (RB1 and CDK2), and cellular differentiation (KRT8). Their expression profiles were investigated by RT-qPCR and were correlated to immunohistochemically based molecular subtypes and BC clinical and pathological features. The differential expression of several genes in the primary tumor tissue was related to the LN involvement. Some of those genes, including PIK3CB, RB1, and AKT3, were more expressed in LN- BC patients, while some others, notably ERBB2 and AKT1, in LN+ ones. Among the candidate biomarkers, the expression levels of AKT isoforms influenced also patients' survival rates. In detail, higher expression levels of AKT1 and AKT2 negatively influenced overall patients' survival, and in particular, AKT2 expression levels defined a group of luminal B BC patients with shorter cancer-specific survival. On the contrary, longer cancer-specific survival was recorded in luminal A BC patients with higher expression levels of AKT3. That finding was also confirmed by Cox multivariate analysis. The same AKT3 resulted to be a possible candidate predictive biomarker for Tamoxifen response. In conclusion, our study highlighted the complex regulation of the PI3K/AKT pathway in BC and its differences in BC patients with and without lymph node involvement.Citation to related work
Hindawi LimitedHas part
Disease MarkersADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.eduae974a485f413a2113503eed53cd6c53
http://dx.doi.org/10.34944/dspace/4568