Development of a nine‑lncRNA signature as a novel prognostic marker of estrogen receptor‑negative breast cancer

Abstract

Long non-coding RNAs (lncRNAs) have been demonstrated to be aberrantly expressed in several types of tumor, and dysregulated lncRNAs are suggested to play a prognostic role in breast cancer (BC). Estrogen receptor (ER) status is a prognostic factor in patients with ER-negative BC, which is associated with poor prognosis. Thus, the present study developed a prognostic lncRNA signature specifically for ER-negative BC, in order to predict the risk of post-surgery relapse and improve patient prognosis. A gene expression profile containing 1,631 lncRNAs was obtained by investigating and integrating publicly available cohorts of BC. Subsequently, a nine-lncRNA signature was developed and validated in two independent cohorts via the Cox regression model. Using the nine-lncRNA signature, patients in the discovery cohort were divided into high-and low-risk groups, with significantly different disease-free survival [DFS; hazard ratio (HR)=2.718, 95% confidence interval (CI)=2.115-3.494, P<0.0001]. Receiver operating characteristic curve analyses demonstrated that the area under the curve reached 0.908. Similar results were obtained in the two independent cohorts (HR=1.499, 95% CI=0.950-2.365, P=0.04; HR=1.262, 95% CI=1.056-1.510, P=0.01), respectively. Furthermore, the nine lncRNAs were demonstrated to play important roles in the cell invasion and metastasis of different types of tumor. The differentially expressed genes (DEGs) identified between the high-and low-risk groups were consistently high in the discovery and validation cohorts. Functional analysis indicated that these DEGs, as well as genes co-expressed with the nine lncRNAs, were involved in cancer-associated signaling pathways, all of which provide further evidence for the predictive ability of the nine-lncRNA signature. Overall, the present study developed a novel prognostic biomarker for ER-negative BC.

KDM7A-DT induces genotoxic stress, tumorigenesis, and progression of p53 missense mutation-associated invasive breast cancer

“…Historically, heterogeneity in breast cancer is understood in terms of varying expression of the ER, PR, and HER2. Recent studies have supported the link between miRNAs and lncRNAs and HR expression in patients with BRCA, highlighting their potential as prognostic biomarkers in hormonal-dependent cancers ( 81 – 83 ). In the whole BRCA cohort, KDM7A-DT overexpression is associated with poor BRCA outcomes across the entire BRCA cohort.…”

Upregulation of long noncoding RNA linc02544 and its association with overall survival rate and the influence on cell proliferation and migration in lung squamous cell carcinoma

“…The abnormal expression of linc02544 was reported in several diseases [ 12 , 13 ]. For instance, a study performed RNA sequencing and acquired many differently expressed lncRNAs, mRNAs, and circRNAs in the human hypertrophic scar, in which linc02544 was one of the top three deregulated expression lncRNAs, which may play a central role in hypertrophic scar [ 12 ].…”

“…The aberrant expression of linc02544 was observed in several diseases, such as hypertrophic scars [ 12 ] and breast cancer [ 13 ]. A recent study identified numerous lncRNAs and mRNAs in lung adenocarcinoma, among which include linc02544 [ 14 ].…”