Identification of a novel lncRNA signature for the diagnosis of TNBC basal subtype

TNBC stands out as a particularly aggressive type of breast cancer (BC). Considering this, our prospective study focuses on developing a lncRNA signature that can aid in the diagnosis of the TNBC subtype. Differential expression analysis was performed on the TCGA-BRCA dataset and GEO dataset to identify signature lncRNAs that can diffrentiate between TNBC and non-TNBC. Out of these common 34 DE-lncRNAs, 12 lncRNAs were shortlisted by comparing them with cuproptosis-associated lncRNAs. These candidate lncRNAs were correlated with 100 DE protein-coding genes. After TNBC subtype-specific expression analysis, three novel lncRNAs, LINC01956, LINC02188 and CASC8, were identified that exhibited TNBC-BL1 subtype specific expression. Gene Ontology and KEGG pathway analysis show the involvement of these lncRNAs in cell cycle, cell migration, DNA replication, and angiogenesis. The correlated protein-coding genes (PCGs) were mainly associated with NF-kappa B, Wnt, SP1, ERbB, signaling pathways. The expression of these candidate lncRNAs was validated in paraffin-embedded tissue samples (80 paraffin-embedded BC samples with adjacent 80 normal tissues) revealing their upregulation in TNBC. To assess their potential as a circulating biomarker, expression analysis was performed from blood (80 BC patient blood, 40 normal individuals) and serum (40 serum samples from BC patients and 40 serum samples from normal individuals), revealing their upregulation in TNBC as compared to the control Moreover, the expression of this lncRNA signature was carried out in basal-specific BC cell lines. Elevated expression of these lncRNAs validated their basal-specific expression. The diagnostic efficacy of these candidate lncRNA signatures was further determined by ROC curve analysis. High expression of these lncRNA individually showed AUC value ≥ 0.8 and significant p-value verified their potential to be used as diagnostic biomarker particularly for TNBC. LncRNA signature displayed an AUC value of 0.8604 at 95%CI: 0.8041–0.9099 with corresponding sensitivity of 83.67% and specificity of 96.92% in TNBC vs. control. Thus, the present study provides three lncRNAs-based signatures for TNBC-BL1 subtype diagnosis.