Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

Abstract

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease

“…It is worth noting that NNT-AS1 was down-regulated in studies [34,[37][38][39] on ovarian cancer, triple-negative breast cancer, and gastric cancer, which is inconsistent with the results of the others [32,33,35,36]. These differences need to be further verified in large-scale experiments, and the connection between NNT-AS1 and sex hormones and sex hormone receptors deserves more in-depth exploration.…”

“…This suggests that the expression of NNT-AS1 may be related to sex hormone receptors. A recent bioinformatics study based on Gene Expression Omnibus (GEO) data analyzed the expression of lncRNA in triple-negative breast cancer (including ER-negative), in which NNT-AS1 was also found to be down-regulated [38]. In addition, in a study on ovarian cancer, the low level of NNT-AS1 was confirmed as well [39].…”

Identification of NUF2 and FAM83D as potential biomarkers in triple-negative breast cancer

“…A recent study found that CHD4-β1 integrin axis may be a prognostic marker for TNBC using next-generation sequencing and bioinformatics analysis ( Ou-Yang et al, 2019 ). The computational analysis of complex biological networks could help research scholars identify potential genes related to TNBC ( Li et al, 2020 ).…”

Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells

“…A few other lncRNAs also showed methylation level changes: DOCK4-AS1, LINC00911, and RFX3-AS1 were hypermethylated, whereas STXBP5-AS1 and LINC01477 were hypomethylated. Notably, LINC00911 and RFX3-AS1 are known as oncogenes [ 17 , 32 ], whereas STXBP5-AS1 is known as a tumor suppressor [ 33 ]. These findings suggest that the tumor-suppressive activity of Rg3 could be attributed in part to its epigenetic regulation of tumor-related lncRNAs.…”