Abstract
Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer.
Highlights
The results show elevation of HERV-K expression exclusively in the basal subtype, perhaps associated with extremely poor prognosis and high frequencies of recurrence and metastasis
Because HERV-K is not observed in normal cells, it might be an excellent target for cancer vaccines against basal breast cancer, or for immunotherapy
We have recently described therapeutic antibodies against HERV-K14
Summary
HERV-K is overexpressed in basal breast cancer. In previous studies it was reported that HERV-K is overexpressed in breast cancer. The analysis of this ILC/other dataset, which was predominately non-IDC, suggests that HERV-K associations with CDK6/Rb phosphorylation/E2F transcription factor release/ derepression of S-phase genes, which was discussed in greater detail above, might be relevant in IDC, whereas HERV-K effects on Ras mutation status, and on β-catenin, E-cadherin, CDK4, and TK1 abundance may be important in all breast cancer types These results give us a starting point to pursue mechanistic studies that are unique to HERV-K involvement in basal breast cancer patients with IDC, but not in those with ILC or other breast cancer types. This study illustrates the value of TCGA data for discovery of novel biomarkers and for formulation of novel hypotheses, including hypotheses that may be useful in the attack on this aggressive subtype of breast cancer
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