Long non-coding RNA, LINC01614 as a potential biomarker for prognostic prediction in breast cancer

PeerJ. 2019 Nov 14:7:e7976. doi: 10.7717/peerj.7976. eCollection 2019.

Abstract

Background: 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.

Methods: 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.

Results: We found that a total of 398 lncRNAs were significantly differentially expressed between BRCA and adjacent normal tissues (adjusted P value <= 0.0001 and |logFC| >= 1). Additionally, 381 potential lncRNAs were correlated Overall Survival (OS) (P 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.

Conclusions: 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.

Keywords: Biomarker; Breast cancer; LncRNA; Survival.

Grants and funding

This work was supported by grants from the Shanghai Pudong New Area Health and Family Planning Commission Health Science and Technology Project, NO# PW2016B-5. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.