Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37203, USA.
Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, 250033, Shandong, People's Republic of China.
Breast Cancer Res Treat. 2021 Apr;186(3):769-777. doi: 10.1007/s10549-020-06021-6. Epub 2020 Nov 27.
Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication.
To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS).
Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05).
Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.
长链非编码 RNA(lncRNA)越来越被认为是乳腺癌发病机制和/或预后的重要调节因子,包括三阴性乳腺癌(TNBC)亚型。然而,以前很少有研究使用 RNA 测序(RNA-Seq)技术,也没有研究进行独立的复制。
为了系统评估 lincRNA 表达与 TNBC 生存之间的关联,我们使用来自上海乳腺癌生存研究(SBCSS)和南方社区队列研究(SCCS)的 200 例 TNBC 患者的 RNA-Seq 数据检测了 TNBC 组织中的 lincRNA 表达谱。
发现 25 个 lincRNA 与总生存相关(P<0.05,Q 统计量无显著异质性 P>0.1),61 个 lincRNA 与无病生存(DFS)相关。其中,两个 lincRNA(LINC01270 和 LINC00449)与总生存和 DFS 均显著相关,并且在肿瘤组织中的表达明显高于相邻正常乳腺组织(log[Fold Change]>0.5, FDR<0.05)。我们进一步使用体外功能实验评估了 LINC01270 和 LINC00449 的潜在功能,发现 siRNA 介导的 LINC01270 和 LINC00449 表达下调显著降低了 TNBC 细胞的活力、集落形成和细胞迁移能力(P<0.05)。
观察性研究和体外实验的证据表明,LINC00449 和 LINC01270 可能是 TNBC 的预后生物标志物。