A Novel Prognostic Signature of mRNA-lncRNA in Breast Cancer

被引:7
|
作者
Liu, Qiang [1 ]
Wang, Zhongzhao [1 ]
Kong, Xiangyi [1 ]
Wang, Xiangyu [1 ]
Qi, Yihang [1 ]
Gao, Ran [1 ]
Fang, Yi [1 ]
Wang, Jing [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Dept Breast Surg Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China
基金
中国国家自然科学基金;
关键词
breast cancer; lncRNA; mRNA; prognostic signature; RNA-seq; LONG NONCODING RNA; HOTAIR; ASSOCIATION; MUTATIONS; PACKAGE; TARGET; PIK3CA; TESTS; TBX2;
D O I
10.1089/dna.2019.5223
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Comprehensive genomic testing will be required to identify appropriate targets for the precision therapy of breast cancer. Although RNA sequencing (RNA-seq) is an unparalleled platform for this purpose, existing molecular-based prognostic signatures are not optimal for RNA-seq data. In this study, we analyzed RNA-seq datasets to generate a novel prognostic gene signature for breast cancer patients. RNA-seq and clinical datasets from breast cancer patients were obtained from The Cancer Genome Atlas and randomly assigned to training (n = 379) and test (n = 378) cohorts. Using the training cohort, sequential univariate Cox analysis, robust likelihood-based survival analysis, and stepwise multivariable Cox analysis identified a five-gene signature composed of one long noncoding RNA gene and four protein-coding genes. The five-gene signature was then used to dichotomize patients into risk groups and validated using Kaplan-Meier and multivariable Cox analyses. In the full test cohort, the high-risk group had worse overall survival (hazard ratio [HR] = 4.74, 95% confidence interval [CI] = 2.33-9.64, p < 0.0001) and worse relapse-free survival (HR = 2.26, 95% CI = 1.11-4.61, p = 0.024) than the low-risk group. Similarly, overall survival was worse in the high-risk group within nearly all clinically important subsets, including early stage disease (I/II) (HR = 7.87, 95% CI = 3.69-16.77, p < 0.0001), and luminal A (HR = 4.23, 95% CI = 1.11-16.12, p = 0.034), luminal B (HR = 12.79, 95% CI = 2.74-59.69, p = 0.001), and basal (HR = 18.11, 95% CI = 3.21-102.05, p = 0.001) subtypes. Notably, the five-gene signature exhibited superior prognostic performance compared with the Oncotype DX 21-gene signature. This novel five-gene signature may therefore be a powerful prognostic tool for personalized treatment of breast cancer patients as part of an integrated RNA-seq clinical sequencing program.
引用
收藏
页码:671 / 682
页数:12
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