Integrative single-cell transcriptomics and co-expression network analysis identify SIMALR as a prognostic immune-related lncRNA in breast cancer: in silico analysis and validation

Abstract

This study aimed to identify and characterize irlncRNAs associated with prognosis and immune modulation in breast cancer. We integrated single-cell RNA sequencing, hdWGCNA, and bulk RNA-seq differential expression analysis results to identify candidate irlncRNAs. The top candidate, SIMALR, was further investigated using immune, survival, mutation analysis, and GSEA. RT-qPCR preliminary validation was performed on patient tissues. SIMALR was linked to favorable survival and enriched in immune pathways, including T-cell receptor signaling, Natural Killer (NK) cell cytotoxicity, and antigen processing. Pearson analysis showed co-expression of SIMALR-related genes (CD8A, CD4, TNF, LCP2, ITGB2) in key immune populations. High SIMALR As per standard instruction, "Statement of Significance" section should not be captured. Hence, the "Clinical significance" section was deleted. Please check and confirm if presented correctly; otherwise, please amend. expression in tumor cells is associated with enhanced secretion of Th1-attracting chemokines (CXCL9/10/11, CCL5), recruitment of CD8 + T cells, activated dendritic cells, and both M1/M2 macrophages. RT-qPCR confirmed higher SIMALR expression in tumors. Due to limited availability of clinical specimens, the RT-qPCR analysis was performed on paired tissue samples from six patients, and therefore the results should be considered a preliminary validation. SIMALR may contribute to anti-tumor immunity, highlighting its potential as a promising biomarker and therapeutic target in breast cancer.