Dataset Information

A Potential Prognostic Long Noncoding RNA Signature to Predict Recurrence among ER-positive Breast Cancer Patients Treated with Tamoxifen.

ABSTRACT: Limited predictable long noncoding RNA (lncRNA) signature was reported in tamoxifen resistance among estrogen receptor (ER)-positive breast cancer (BC) patients. The aim of this study was to identify and assess prognostic lncRNA signature to predict recurrence among ER-positive BC patients treated with tamoxifen. Cohorts from Gene Expression Omnibus (GEO) (n?=?298) and The Cancer Genome Atlas (TCGA) (n?=?160) were defined as training and validation cohort, respectively. BC relapse associated lnRNAs was identify within training cohort, and the predictable value of recurrence was assessed in both cohorts. A total of 11lncRNAs were recognized to be associated with relapse free survival (RFS) of ER-positive BC patients receiving tamoxifen, who were divided into low-risk and high-risk group on basis of relapse risk scores (RRS). Multivariate cox regression analyses revealed that the RRS is an independent prognostic biomarker in the prediction of ER-positive BC patients' survival. GSEA indicated that high-risk group was associated with several signaling pathways in processing of BC recurrence and metastasis such as PI3K-Akt and Wnt signaling. Our 11-lncRNA based classifier is a reliable prognostic and predictive tool for disease relapse in BC patients receiving tamoxifen.

SUBMITTER: Wang K

PROVIDER: S-EPMC5816619 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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A Potential Prognostic Long Noncoding RNA Signature to Predict Recurrence among ER-positive Breast Cancer Patients Treated with Tamoxifen.

Wang Kang K Li Jie J Xiong Yong-Fu YF Zeng Zhen Z Zhang Xiang X Li Hong-Yuan HY

Scientific reports 20180216 1

Limited predictable long noncoding RNA (lncRNA) signature was reported in tamoxifen resistance among estrogen receptor (ER)-positive breast cancer (BC) patients. The aim of this study was to identify and assess prognostic lncRNA signature to predict recurrence among ER-positive BC patients treated with tamoxifen. Cohorts from Gene Expression Omnibus (GEO) (n = 298) and The Cancer Genome Atlas (TCGA) (n = 160) were defined as training and validation cohort, respectively. BC relapse associated lnR ...[more]

PMID: 29453409

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Project description:PurposeRecent 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.MethodsLncRNA 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.ResultsSix 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.ConclusionThis 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.

Project description:The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.

Project description:BackgroundCurrent clinical risk factors stratify patients with neuroblastoma (NB) for appropriate treatments, yet patients with similar clinical behaviors evoke variable responses. MYCN amplification is one of the established drivers of NB and, when combined with high-risk displays, worsens outcomes. Growing high-throughput transcriptomics studies suggest long noncoding RNA (lncRNA) dysregulation in cancers, including NB. However, expression-based lncRNA signatures are altered by MYCN amplification, which is associated with high-risk, and patient prognosis remains limited.MethodsWe investigated RNA-seq-based expression profiles of lncRNAs in MYCN status and risk status in a discovery cohort (n = 493) and validated them in three independent cohorts. In the discovery cohort, a prognostic association of lncRNAs was determined by univariate Cox regression and integrated into a signature using the risk score method. A novel risk score threshold selection criterion was developed to stratify patients into risk groups. Outcomes by risk group and clinical subgroup were assessed using Kaplan-Meier survival curves and multivariable Cox regression. The performance of lncRNA signatures was evaluated by receiver operating characteristic curve. All statistical tests were two-sided.ResultsIn the discovery cohort, 16 lncRNAs that were differentially expressed (fold change ≥ 2 and adjusted P ≤ 0.01) integrated into a prognostic signature. A high risk score group of lncRNA signature had poor event-free survival (EFS; P < 1E-16). Notably, lncRNA signature was independent of other clinical risk factors when predicting EFS (hazard ratio = 3.21, P = 5.95E-07). The findings were confirmed in independent cohorts (P = 2.86E-02, P = 6.18E-03, P = 9.39E-03, respectively). Finally, the lncRNA signature had higher accuracy for EFS prediction (area under the curve = 0.788, 95% confidence interval = 0.746 to 0.831).ConclusionsHere, we report the first (to our knowledge) RNA-seq 16-lncRNA prognostic signature for NB that may contribute to precise clinical stratification and EFS prediction.

Dataset Information

A Potential Prognostic Long Noncoding RNA Signature to Predict Recurrence among ER-positive Breast Cancer Patients Treated with Tamoxifen.

Publications

A Potential Prognostic Long Noncoding RNA Signature to Predict Recurrence among ER-positive Breast Cancer Patients Treated with Tamoxifen.

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