Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor-Positive Breast Cancer Patients Treated with Tamoxifen.
Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor-Positive Breast Cancer Patients Treated with Tamoxifen.
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接受他莫昔芬治疗的雌激素受体阳性乳腺癌患者的长非编码 RNA 特征和疾病结果。
DOI：
10.4048/jbc.2018.21.e39
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发表时间：
2018-09
影响因子：
2.4
通讯作者：
Shen K
中科院分区：
文献类型：
--
作者：
Wang G;Chen X;Liang Y;Wang W;Fang Y;Shen K
最近的数据表明，在雌激素受体(ER)阳性的乳腺癌中，长非编码RNA(LncRNAs)的表达水平与他莫昔芬的敏感性有关。在此，我们构建了一个基于lncRNA的模型来预测接受他莫昔芬治疗的ER阳性乳腺癌患者的疾病结局。通过重新定位接受三苯氧胺治疗的ER阳性乳腺癌患者的现有微阵列，从基因表达总览中获得LncRNA表达信息。无远处转移生存期(DMFS)的预测信号随后被建立在发现队列患者的Cox比例风险回归模型的基础上，该模型在另一个独立的验证数据集中被进一步评估。在DISCOVER队列中，发现6个lncRNA与DMF相关，用于构建他莫昔芬疗效相关的lncRNA签名(TLS)。在DISCOVER队列中，分别有133名和362名具有TLS高风险和低风险特征的患者。单变量和多变量分析均显示TLS与DMFS相关。与低风险患者相比，高风险患者的预后更差，风险比为4.04(95%可信区间为2.83-5.77；p<；0.001)。亚组分析和受试者操作特征分析均显示，TLS在淋巴结阴性、腔内B、21基因复发评分高危、70基因预后标志性高危患者中表现较好。此外，在21个基因复发评分和70个基因预后标志的比较中，TLS在所有患者的受试者工作特征曲线下显示相似的面积。基因集浓缩分析显示，TLS高危患者与低危患者表现出不同的细胞周期和核苷酸代谢相关基因表达模式。这种6-lncRNA签名与接受他莫昔芬治疗的ER阳性乳腺癌患者的疾病结局有关，这与以前的信使RNA签名相当，需要进一步的临床评估。
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. 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. 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. 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.
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
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影响因子：
4.6
作者：
Zhou M;Zhong L;Xu W;Sun Y;Zhang Z;Zhao H;Yang L;Sun J
通讯作者：
Sun J
影响因子：
8
作者：
Xue X;Yang YA;Zhang A;Fong KW;Kim J;Song B;Li S;Zhao JC;Yu J
通讯作者：
Yu J
影响因子：
5.8
作者：
Jiang, Hui;Wong, Wing Hung
通讯作者：
Wong, Wing Hung
影响因子：
5.8
作者：
Gendoo, Deena M. A.;Ratanasirigulchai, Natchar;Haibe-Kains, Benjamin
通讯作者：
Haibe-Kains, Benjamin