EVALUATION OF THE EXPRESSION OF TRANSPOSABLE ELEMENTS AS BREAST CANCER BIOMARKERS

Breast cancer is a complex and heterogeneous disease. It represents a challenge for personalized medicine strategies, especially for triple-negative breast cancer (TNBC), due to its unfavorable prognosis, recurrence, and lack of therapeutic targets. In this context, new biomarkers have been studied to improve the understanding of the disease and enable better patient outcomes. Transposable elements (TEs) are repetitive and mobile sequences of the human genome. It is divided into DNA transposons and retrotransposons, such as the long-interspersed element-1 (L1) and human endogenous retroviruses (HERVs). The literature has described associations between the expression of some of these elements and cancer; however, a more comprehensive understanding of their clinical significance is still limited. This work aims to evaluate the expression of transposable elements and their potential as biomarkers and possible therapeutic targets in breast cancer, with locus-specific resolution. Using transcriptomic data, we evaluated breast cancer patient cohorts to verify the presence of TE, associate their transcripts with clinical outcomes, and verify their potential as biomarkers and possible therapeutic targets in breast cancer. Our institutional cohort comprises transcriptomics from young 36 TNBC cases, including 8 cases with tumors after neoadjuvant chemotherapy treatment. We identified differentially expressed TEs (DETEs) in cancer and healthy tissue in public datasets, with the L1 class the most affected. In our cohort, DETEs were identified in tumor tissue before and after neoadjuvant chemotherapy treatment (NAC), being class L1 in our cohort and in GSE260693 was “Others” (not Class 1, Class 2, Class 3, nor L1) and Class 1. Also, differentially expressed genes (DEGs) were associated with the immune system and epithelial-mesenchymal transition (EMT), and cancer-related pathways. Between the DETEs from our cohort, we found that their expression had a strong correlation with intersect genes, one of which was ZEB1, involved in EMT, and the immune cell marker genes CD48 and CD38, evidencing a possible expression common control. We also found that these DETEs were located at cis-regulatory regions of genes, but not enriched. L1 class was also linked to response to neoadjuvant chemotherapy and early relapse. We investigated the immune infiltrate in the response analysis and found that dendritic cells (activated) were significantly higher in complete responders, and B cells (pro) in non-complete responders' samples by in silico analysis. In conclusion, TEs are expressed in breast cancer; their expression is modulated by neoadjuvant therapy and can be associated with response to therapy.