Abstract
Estrogen receptor signalling plays important regulatory roles in multiple mammalian physiological processes. Dysregulation of estrogen receptor (ER) expression and/or its associated signalling pathway is strongly associated with the development, progression, transition, and endocrine-resistance of breast cancer. Non-coding transcripts are essential regulators of almost every level of gene regulation. However, few long non-coding transcripts (lncRNAs) associated with the estrogen receptor signalling pathway have been well-described. We used array-based methods to identify 33 estrogen receptor agitation-related (ERAR) lncRNAs. A coding–non-coding gene co-expression network analysis suggested that 15 ERAR lncRNAs were associated with mitosis, DNA damage, and DNA repair. Kaplan–Meier analysis indicated that five ERAR lncRNAs selected using the Random Forest-Recursive Feature Elimination algorithm were significantly correlated with endocrine resistance-free survival and distant metastasis-free survival as well as disease free survival. Our results suggest that ERAR lncRNAs may serve as novel biomarkers for guiding breast cancer treatment and prognosis. Furthermore, our findings reveal a new avenue by which estrogen receptor signalling can be further explored.
Highlights
A gene co-expression network can be modelled as an undirected graph in which each node represents a gene, while each edge represents the co-expression relationship between a gene pair[12]
We conducted a survival analysis and found that the expression profiles of some estrogen receptor agitation-related (ERAR) lncRNAs were significantly correlated with endocrine resistance-free survival and distant metastasis-free survival of estrogen receptor-positive (ER+)breast cancer patients
We investigated whether ERAR lncRNA genes were of clinical importance by conducting Kaplan–Meier survival analysis on 164 ER+breast cancer patients
Summary
Estrogen receptor alpha agitation-related (ERAR) lncRNA genes. The MCF-7 cell line has been widely used to study estrogen signalling. We parsed the topology of the whole co-expression network into separated hub-bused subnetworks and identified 15 ERAR lncRNA genes that met the above criteria (corrected P value > 0.93) (Figure S2, Table S6) These genes were significantly (cumulative hypergeometric P-values16,26
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