Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor-Positive Breast Cancer Patients Treated with Tamoxifen / 한국유방암학회지
Journal of Breast Cancer
; : 277-287, 2018.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-716748
Responsible library:
WPRO
ABSTRACT
PURPOSE:
Recent data have shown that the expression levels of long noncoding RNAs (lncRNAs) are associated with tamoxifen sensitivity in estrogen receptor (ER)-positive breast cancer. Herein, we constructed an lncRNA-based model to predict disease outcomes of ER-positive breast cancer patients treated with tamoxifen.METHODS:
LncRNA expression information was acquired from Gene Expression Omnibus by re-mapping pre-existing microarrays of patients with ER-positive breast cancer treated with tamoxifen. The distant metastasis-free survival (DMFS) predictive signature was subsequently built based on a Cox proportional hazard regression model in discover cohort patients, which was further evaluated in another independent validation dataset.RESULTS:
Six lncRNAs were found to be associated with DMFS in the discover cohort, which were used to construct a tamoxifen efficacy-related lncRNA signature (TLS). There were 133 and 362 patients with TLS high- and low-risk signatures in the discover cohort. Both univariate and multivariate analysis demonstrated that TLS was associated with DMFS. TLS high-risk patients had worse outcomes than low-risk patients, with a hazard ratio of 4.04 (95% confidence interval, 2.83–5.77; p < 0.001). Both subgroup analysis and receiver operating characteristic analysis indicated that TLS performed better in lymph node-negative, luminal B, 21-gene recurrence score high-risk, and 70-gene prognosis signature high-risk patients. Moreover, in a comparison of the 21-gene recurrence score and 70-gene prognosis signature, TLS showed a similar area under receiver operating characteristic curve in all patients. Gene Set Enrichment Analysis indicated that TLS high-risk patients showed different gene expression patterns related to the cell cycle and nucleotide metabolism from those of low-risk patients.CONCLUSION:
This six-lncRNA signature was associated with disease outcome in ER-positive breast cancer patients treated with tamoxifen, which is comparable to previous messenger RNA signatures and requires further clinical evaluation.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Phenobarbital
/
Prognosis
/
Recurrence
/
Tamoxifen
/
Breast
/
Breast Neoplasms
/
RNA, Messenger
/
Gene Expression
/
Cell Cycle
/
Multivariate Analysis
Type of study:
Etiology study
/
Incidence study
/
Observational study
/
Prognostic study
/
Risk factors
Limits:
Humans
Language:
English
Journal:
Journal of Breast Cancer
Year:
2018
Document type:
Article