Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

Abstract

Breast cancer (BRCA) is the most leading cause of cancer worldwide. It is a heterogeneous disease with at least five molecular subtypes including luminal A, luminal B, basal-like, HER2-enriched, and normal-like. These five molecular subtypes are usually stratified according to their mRNA profile patterns; however, ncRNAs are increasingly being used for this purpose. Among the ncRNAs class, the long non-coding RNAs (lncRNAs) are molecules with more than 200 nucleotides with versatile regulatory roles; and high tissue-specific expression profiles. The heterogeneity of BRCA can also be reflected regarding tumor microenvironment immune cells composition, which can directly impact a patient’s prognosis and therapy response. Using BRCA immunogenomics data from a previous study, we propose here a bioinformatics approach to include lncRNAs complexity in BRCA molecular and immune subtype. RNA-seq data from The Cancer Genome Atlas (TCGA) BRCA cohort was analyzed, and signal-to-noise ratio metrics were applied to create these subtype-specific signatures. Five immune-related signatures were generated with approximately ten specific lncRNAs, which were then functionally analyzed using GSEA enrichment and survival analysis. We highlighted here some lncRNAs in each subtype. LINC01871 is related to immune response activation and favorable overall survival in basal-like samples; EBLN3P is related to immune response suppression and progression in luminal B, MEG3, XXYLT1-AS2, and LINC02613 were related with immune response activation in luminal A, HER2-enriched and normal-like subtypes, respectively. In this way, we emphasize the need to know better the role of lncRNAs as regulators of immune response to provide new perspectives regarding diagnosis, prognosis and therapeutical targets in BRCA molecular subtypes.

Long Non-Coding RNAs Associated with Ribosomes in Human Adipose-Derived Stem Cells: From RNAs to Microproteins

“…Similarly, EBLN3P promotes the recovery of impaired spiral ganglion neurons by competitively binding miR-204-5p, regulating TMPRSS3 expression [78]. Despite showing a regulatory function in different cancer types [79,80], here we demonstrated a coding capacity of EBLN3P in hASC, which represents a possible dual-function of this transcript in stem cell biology, including a putative secreted smORF-derived microprotein.…”

The Role of lncRNA in the Development of Tumors, including Breast Cancer

“…EBLN3P is associated with immune response suppression and progression in the luminal B subtype, and MEG3, XXYLT1-AS2, and LINC02613 are associated with activation of immune response in luminal A, HER2-enriched, and normal-like subtypes, respectively. Further research is needed to better understand the role of lncRNAs as regulators of the immune response to provide new perspectives on diagnosis, prognosis, and therapeutic targets for the molecular subtypes of BRCA [49].…”

Identification of gene signatures for COAD using feature selection and Bayesian network approaches

“…The current study aimed to identify gene signatures that could be used to classify COAD samples and normal colon tissues. Specifically, we established a feature selection model, SNR-PPFS, by combining the signal-to-ratio (SNR) ranking algorithm 17 , 18 with the predictive permutation feature selection (PPFS) algorithm, a Markov blanket (MB) based feature subset selection method. The PPFS algorithm considers features both individually and collectively in order to provide the best set of features.…”