linc00673 (ERRLR01) is a prognostic indicator of overall survival in breast cancer

LncRNAs are novel noncoding RNAs involved in the epigenetic regulation of gene expression by recruiting ribonucleoprotein complexes to specific genomic loci to initiate histone methylation and/or other chromatin modifications. LncRNAs themselves function as tumor suppressors or oncogenes, depending on the gene regulatory networks they govern. We identified lnc00673 (ERRLR01) as a marker of overall survival (OS) in breast cancer patients. Specifically, ERRLR01 levels were elevated in triple-negative breast cancer (TNBC) as compared with Luminal-A, Luminal-B, and HER2 breast cancer subtypes. ERRLR01 levels were also inversely correlated with breast cancer survival across all breast cancer patients. Upon stratification, OS in ERα− tumors correlated with negative overall survival, while in ERα+ tumors, ERRLR01 correlated with positive outcomes. This suggests ERRLR01 is modulated by hormone signaling in breast cancer. Gene-network analysis revealed ERRLR01 correlated with distinct pathways including “epithelial development” and “cellular differentiation.” These data suggest ERRLR01 operates as an oncogene in TNBC, as well as a biomarker in breast cancer patients.

长链非编码RNA（LncRNAs）是一类新型非编码RNA，可通过将核糖核蛋白复合物招募至特定基因组位点以启动组蛋白甲基化及/或其他染色质修饰，参与基因表达的表观遗传调控。LncRNAs本身可作为抑癌基因或致癌基因，具体取决于其所调控的基因调控网络。本研究鉴定出lnc00673（ERRLR01）可作为乳腺癌患者总生存期（overall survival, OS）的标志物。具体而言，与腔面A型、腔面B型及人表皮生长因子受体2（HER2）过表达型乳腺癌亚型相比，三阴性乳腺癌（triple-negative breast cancer, TNBC）组织中ERRLR01的表达水平显著升高。在全部乳腺癌患者中，ERRLR01的表达水平与乳腺癌总生存期呈负相关。经分层分析后发现，在雌激素受体α（estrogen receptor α, ERα）阴性肿瘤中，ERRLR01表达与不良总生存期相关；而在雌激素受体α阳性肿瘤中，ERRLR01表达则与良好预后相关。上述结果提示，ERRLR01的表达可受乳腺癌激素信号通路调控。基因网络分析显示，ERRLR01与"上皮发育"及"细胞分化"等多条特异性通路显著相关。以上数据表明，ERRLR01既可作为三阴性乳腺癌中的致癌基因，亦可作为乳腺癌患者的潜在生物标志物。