Exosomal lncRNAs HOTAIR, HULC, and ANRIL: Decoding the Biomarker Landscape of Sporadic Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC/18-21%) lacks targeted treatment options due to the lack of ER/PR and HER2 expression. The transport of lncRNAs via exosomes plays a role in tumor progression and metastasis and reshapes tumor-associated signaling pathways. This study aimed to compare the expression of exosomal HOTAIR, NEAT1, MALAT1, AFAP1-AS1, ANRIL, and HULC lncRNAs in primary tumor tissue and blood of patients with sporadic TNBC to evaluate their potential as biomarkers. The patients diagnosed with TNBC between the years 2021 and 2025, 21 of 62 (33.87%) with sporadic breast cancer and thirty healthy controls were included in the study. Primary tumor tissue and peripheral venous blood samples were collected from 21 patients who did not receive neoadjuvant chemotherapy. Expression levels of exosomal lncRNAs (HOTAIR, NEAT1, MALAT1, AFAP1-AS1, ANRIL, and HULC) were determined in both tissues and blood samples from the patient and control groups using Real-Time PCR method. In the patient group, HOTAIR, HULC, ANRIL, and AFAP1_AS1 gene expression was lower (downregulated) in tissue and serum compared to the control group, whereas NEAT1 and MALAT1 were higher (upregulated). Tissue and serum samples taken from the patient group were found to have statistically consistent expression levels of HOTAIR, HULC, and ANRIL genes. Furthermore, HOTAIR, HULC, and ANRIL serve as biomarkers and can be studied using exosomal RNA samples obtained from patient serum without invasive procedures. Our current study, which has different lncRNA expression profiles, reflects the biological heterogeneity of TNBC and contributes to a better understanding of its subtypes at the molecular level.