Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor-Positive Breast Cancer Patients Treated with Tamoxifen.
- Author:
Gen WANG
1
;
Xiaosong CHEN
;
Yue LIANG
;
Wei WANG
;
Yan FANG
;
Kunwei SHEN
Author Information
- Publication Type:Original Article
- Keywords: Breast neoplasms; Long noncoding RNA; Neoplasm metastasis; Prognosis; Tamoxifen
- MeSH: Breast Neoplasms*; Breast*; Cell Cycle; Cohort Studies; Dataset; Estrogens*; Gene Expression; Humans; Metabolism; Multivariate Analysis; Neoplasm Metastasis; Phenobarbital; Prognosis; Recurrence; RNA, Long Noncoding*; RNA, Messenger; ROC Curve; Tamoxifen*
- From:Journal of Breast Cancer 2018;21(3):277-287
- CountryRepublic of Korea
- Language:English
- 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.
