Abstract
Long non‐coding RNAs (lncRNAs), which competitively bind miRNAs to regulate target mRNA expression in the competing endogenous RNAs (ceRNAs) network, have attracted increasing attention in breast cancer research. We aim to find more effective therapeutic targets and prognostic markers for breast cancer. LncRNA, mRNA and miRNA expression profiles of breast cancer were downloaded from TCGA database. We screened the top 5000 lncRNAs, top 5000 mRNAs and all miRNAs to perform weighted gene co‐expression network analysis. The correlation between modules and clinical information of breast cancer was identified by Pearson's correlation coefficient. Based on the most relevant modules, we constructed a ceRNA network of breast cancer. Additionally, the standard Kaplan‐Meier univariate curve analysis was adopted to identify the prognosis of lncRNAs. Ultimately, a total of 23 and 5 modules were generated in the lncRNAs/mRNAs and miRNAs co‐expression network, respectively. According to the Green module of lncRNAs/mRNAs and Blue module of miRNAs, our constructed ceRNA network consisted of 52 lncRNAs, 17miRNAs and 79 mRNAs. Through survival analysis, 5 lncRNAs (AL117190.1, COL4A2‐AS1, LINC00184, MEG3 and MIR22HG) were identified as crucial prognostic factors for patients with breast cancer. Taken together, we have identified five novel lncRNAs related to prognosis of breast cancer. Our study has contributed to the deeper understanding of the molecular mechanism of breast cancer and provided novel insights into the use of breast cancer drugs and prognosis.
Highlights
Breast cancer, the most frequently diagnosed carcinoma, is the deadli‐ est form of cancer affecting women worldwide.[1]
We constructed a competing endogenous RNAs (ceRNAs) network of patients with breast cancer based on Long non‐coding RNAs (lncRNAs)‐ miRNA‐messenger RNAs (mRNAs) interactions to identify potential prognostic lncRNA biomarkers and understand the regulatory mechanisms at a deep level
We conclude that AL117190.1, COL4A2‐ AS1, LINC00184, Maternally expressed gene 3 (MEG3) and miR‐22 host gene (MIR22HG) act as prognostic biomark‐ ers, whose low expression revealed that patients with breast cancer have better overall survival
Summary
The most frequently diagnosed carcinoma, is the deadli‐ est form of cancer affecting women worldwide.[1] According to the sta‐ tistics of the American Cancer Society, more than 268 600 new cases of invasive breast cancer will be diagnosed in 2019, and approximately 41 760 death cases are expected.[2] Currently, multiple ther‐ apeutic measures are employed, such as chemotherapy, surgery, ra‐ diotherapy, endocrine therapy and targeted therapy,[3] the majority of breast cancers remain incurable This highlights the urgent need for identifying the molecules that have an inhibitory role or facil‐ itating role in tumours, determining novel relevant treatment targets and further improving the treatment and prognosis of patients with breast cancer. We selected lncRNAs, mRNAs and miR‐ NAs whose expression levels were in the top 5000 among the 112 matched specimen pairs Afterwards, these data were used to con‐ struct a co‐expression network to determine the module related to the clinical trait. Findings from our study contribute to further understanding of the molecular mechanisms, biological processes and treatment targets of lncRNAs in the field of breast cancer research
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