紫杉烷
三阴性乳腺癌
肿瘤科
乳腺癌
内科学
医学
比例危险模型
转录组
基因签名
生物标志物
癌症
紫杉醇
癌症研究
生物信息学
生物
基因表达
基因
生物化学
作者
Yi-Zhou Jiang,Yi‐Rong Liu,Xiao‐En Xu,Xi Jin,Xin Hu,Ke‐Da Yu,Zhi‐Ming Shao
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2016-02-27
卷期号:76 (8): 2105-2114
被引量:177
标识
DOI:10.1158/0008-5472.can-15-3284
摘要
Abstract While recognized as a generally aggressive disease, triple-negative breast cancer (TNBC) is highly diverse in different patients with variable outcomes. In this prospective observational study, we aimed to develop an RNA signature of TNBC patients to improve risk stratification and optimize the choice of adjuvant therapy. Transcriptome microarrays for 33 paired TNBC and adjacent normal breast tissue revealed tumor-specific mRNAs and long noncoding RNAs (lncRNA) that were associated with recurrence-free survival. Using the Cox regression model, we developed an integrated mRNA-lncRNA signature based on the mRNA species for FCGR1A, RSAD2, CHRDL1, and the lncRNA species for HIF1A-AS2 and AK124454. The prognostic and predictive accuracy of this signature was evaluated in a training set of 137 TNBC patients and then validated in a second independent set of 138 TNBC patients. In addition, we enrolled 82 TNBC patients who underwent taxane-based neoadjuvant chemotherapy (NCT) to further verify the predictive value of the signature. In both the training and validation sets, the integrated signature had better prognostic value than clinicopathologic parameters. We also confirmed the interaction between the administration of taxane-based NCT and different risk groups. In the NCT cohort, patients in the low-risk group were more likely to achieve pathologic complete remission after taxane-based NCT (P = 0.014). Functionally, we showed that HIF1A-AS2 and AK124454 promoted cell proliferation and invasion in TNBC cells and contributed there to paclitaxel resistance. Overall, our results established an integrated mRNA-lncRNA signature as a reliable tool to predict tumor recurrence and the benefit of taxane chemotherapy in TNBC, warranting further investigation in larger populations to help frame individualized treatments for TNBC patients. Cancer Res; 76(8); 2105–14. ©2016 AACR.
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