Peer Review #2 of "Long non-coding RNA, LINC01614 as a potential biomarker for prognostic prediction in breast cancer (v0.1)"

Abstract

Background Dysregulated lncRNAs may serve as potential biomarkers of cancers including breast cancer. This study aimed to identify lncRNAs with strong prognostic value for breast cancer. Methods LncRNA expression profiles of 929 tissue samples were downloaded from TANRIC database. We performed differential expression analysis between paired breast cancer 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 GSEA. Results We found that a total of 398 lncRNAs were significantly differentially expressed between breast cancer and adjacent normal tissues (adjusted P value <= 0.0001 and |logFC| >=1). Additionally, 381 potential lncRNAs were correlated Overall Survival (P value < 0.05). 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 breast cancer 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 ER+, PR+ and HER2+ subgroup, respectively. Also, breast cancer 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-beta1 response, CDH1 signals and cell adhesion pathways. Conclusions A novel lncRNA LINC01614 was identified as a potential biomarker for prognosis prediction of breast cancer. This study emphasized the importance of LINC01614 and further research should be focused on it.