Microarray Profiling Identifies LINC00974 as a Sensitive Marker for Breast Cancer Risk

Background and Objectives

In the post-genomic era, long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cancers and hold potential as minimally invasive diagnostic biomarkers. This study aimed to perform microarray analysis of the peripheral blood mononuclear cell (PBMC) transcriptome to evaluate differential lncRNA expression in women with luminal A breast cancer.

Methods

A one-color microarray analysis was conducted using SurePrint G3 Human Unrestricted 8×60K arrays and a SureScan Microarray Scanner (Agilent Technologies, USA). The study cohort comprised 16 participants: eight patients diagnosed with luminal A breast cancer and eight healthy controls. Bioinformatic analysis was performed using the "limma" and "tidyverse" packages in the R statistical environment. Functional enrichment analysis was conducted to identify significantly differentially expressed gene clusters. The false discovery rate-adjusted p-value (p_adj) was applied to ensure methodological rigor. Associations between lncRNAs and disease progression were explored using the LncRNADisease 2.0 database.

Results

Differential expression was observed for long intergenic non-coding (LINC), LOC, and antisense RNA genes. Notably, LINC RNA 974 (LINC00974) exhibited significant differential expression (log fold change > |1.5|, p_adj < 0.05) after multiple comparison correction. Analysis using the LncRNADisease 2.0 database revealed associations between LINC and antisense RNAs and other oncological disorders.

Conclusions

This study is the first to demonstrate alterations in the expression levels of lncRNAs in PBMCs of BC patients at early stages (Stage 1–2), supporting their potential as diagnostic markers. The long intergenic non-protein-coding RNA 974 gene (LINC00974) passed FDR correction (LogFC = 1.80; FDR-adjusted p-value [p_adj] = 0.03) and may be considered a sensitive marker for BC risk. Given its role in regulating oncogenic pathways through miRNA sponging and its detectability in peripheral blood, LINC00974 holds promise as a minimally invasive biomarker for early BC diagnosis and potentially as a therapeutic target. These findings are consistent with established concepts of lncRNA functionality, including their roles in gene expression regulation, chromatin remodeling, RNA stabilization, cell proliferation, tumor migration, and metastasis.

The next phase of this work will focus on expanding the sample size and functionally validating the identified lncRNAs. It is essential to assess reproducibility in larger patient cohorts using alternative methods, such as quantitative polymerase chain reaction, to evaluate specific gene expression. Investigating lncRNA expression profiles in PBMCs may provide an informative and minimally invasive cknowlegments approach for studying prevalent BC subtypes.