Wang Yaozong, Song Baorong, Zhu Leilei, Zhang Xia
Department of General Surgery, Hwa Mei Hospital (Ningbo No.2 Hospital), University of Chinese Academy of Sciences, Ningbo, China.
Department of Radiotherapy, Shanghai East Hospital, Tongji University, Shanghai, China.
PeerJ. 2019 Nov 14;7:e7976. doi: 10.7717/peerj.7976. eCollection 2019.
Dysregulated long non-coding RNAs (lncRNAs) may serve as potential biomarkers of cancers including breast cancer (BRCA). This study aimed to identify lncRNAs with strong prognostic value for BRCA.
LncRNA expression profiles of 929 tissue samples were downloaded from TANRIC database. We performed differential expression analysis between paired BRCA and adjacent normal tissues. Survival analysis was used to identify lncRNAs with prognostic value. Univariate and multivariate Cox regression analyses were performed to confirm the independent prognostic value of potential lncRNAs. Dysregulated signaling pathways associated with lncRNA expression were evaluated using gene set enrichment analysis.
We found that a total of 398 lncRNAs were significantly differentially expressed between BRCA and adjacent normal tissues (adjusted value <= 0.0001 and |logFC| >= 1). Additionally, 381 potential lncRNAs were correlated Overall Survival (OS) ( value < 0.05). A total of 48 lncRNAs remained when differentially expressed lncRNAs overlapped with lncRNAs that had prognostic value. Among the 48 lncRNAs, one lncRNA (LINC01614) had stronger prognostic value and was highly expressed in BRCA tissues. LINC01614 expression was validated as an independent prognostic factor using univariate and multivariate analyses. Higher LINC01614 expression was observed in several molecular subgroups including estrogen receptors+, progesterone receptors+ and human epidermal growth factor receptor 2 (HER2)+ subgroup, respectively. Also, BRCA carrying one of four gene mutations had higher expression of LINC01614 including AOAH, CIT, HER2 and ODZ1. Higher expression of LINC01614 was positively correlated with several gene sets including TGF-β1 response, CDH1 signals and cell adhesion pathways.
A novel lncRNA LINC01614 was identified as a potential biomarker for prognosis prediction of BRCA. This study emphasized the importance of LINC01614 and further research should be focused on it.
长链非编码RNA(lncRNA)失调可能是包括乳腺癌(BRCA)在内的多种癌症的潜在生物标志物。本研究旨在鉴定对BRCA具有强预后价值的lncRNA。
从TANRIC数据库下载929个组织样本的lncRNA表达谱。我们对配对的BRCA组织和相邻正常组织进行差异表达分析。采用生存分析来鉴定具有预后价值的lncRNA。进行单因素和多因素Cox回归分析以确认潜在lncRNA的独立预后价值。使用基因集富集分析评估与lncRNA表达相关的失调信号通路。
我们发现BRCA组织和相邻正常组织之间共有398个lncRNA存在显著差异表达(校正P值<=0.0001且|logFC|>=1)。此外,381个潜在lncRNA与总生存期(OS)相关(P值<0.05)。当差异表达的lncRNA与具有预后价值的lncRNA重叠时,共保留48个lncRNA。在这48个lncRNA中,一个lncRNA(LINC01614)具有更强的预后价值,且在BRCA组织中高表达。通过单因素和多因素分析验证LINC01614表达是一个独立的预后因素。在包括雌激素受体阳性、孕激素受体阳性和人表皮生长因子受体2(HER2)阳性亚组等几个分子亚组中均观察到较高的LINC01614表达。此外,携带AOAH、CIT、HER2和ODZ1这四个基因突变之一的BRCA中LINC01614表达较高。LINC01614的高表达与包括转化生长因子-β1反应、CDH1信号和细胞黏附途径等几个基因集呈正相关。
一种新型lncRNA LINC01614被鉴定为BRCA预后预测的潜在生物标志物。本研究强调了LINC01614的重要性,应进一步对其开展研究。