Expression of Human Endogenous Retroviruses (HERVs) in Breast Cancer: A Transcriptomic Study

Background: Human endogenous retroviruses (HERVs) are ancient viral elements inte-grated into the human genome, accounting for approximately 8% of its content. Recent findings suggest that HERVs, especially HERV-K (HML-2), play a significant role in the onset and advancement of breast cancer. Understanding HERV expression patterns could reveal new biomarkers and therapeutic targets in breast cancer. This study examined the expression of endogenous retroviruses in human breast tissues, to reveal potential associations between retroviruses and breast cancer. Methods: RNA-Seq datasets from breast cancer tissues (ductal carcinoma and triple-negative subtypes) and normal breast tissues were retrieved from the NCBI Sequence Read Archive (SRA). Bioinformatics analysis included read mapping against the human genome (hg19) and a custom pseudogenome containing HERV sequences. Normalized expression of HERV-human junctions was calculated and statistical comparisons were performed using independent samples t-tests and Mann-Whitney tests. Results: Breast cancer tissues exhibited signifi-cantly higher normalized coverage of HERV integration sites compared to healthy con-trols (p=0.009). Among breast cancer cases, patients who had undergone treatment showed significantly lower HERV expression than untreated patients (p=0.023). Visuali-zation via IGV confirmed increased read accumulation at HERV loci in cancer samples. Conclusion: This study showed that HERVs are overexpressed in breast cancer tissues compared to normal breast tissues, with expression levels influenced by therapeutic in-terventions. These findings support the potential role of HERVs as biomarkers for breast cancer diagnosis, prognosis, and therapeutic monitoring. Further research is warranted to explore HERV-targeted strategies for breast cancer treatment.