Introduction The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for
immune cell interaction. HLA-G is known for their high immunosuppressive effect and
its potential as predictive marker in breast cancer. However, nothing is known about
the pseudogene HLA-J and its immunosuppressive, prognostic and predictive features.
Material and Methods HLA-J, ESR1, ERBB2, Keratin 5 and 20 mRNA expression was analysed in 29 fresh frozen
breast cancer biopsies and its corresponding restates obtained from patients treated
with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based
Primer/Probe sets and normalised to Calmodulin2.
Results All breast cancer samples did express HLA-J and showed an upregulation after NACT.
HLA-J was significantly associated with overexpression of the ESR1 mRNA status (Spearman
Rho 0,5679; p = 0.0090) and KRT5 mRNA (Spearman Rho 0,6121; p = 0.0041) in breast
cancer core biopsies. Elevated post-therapy mRNA expression of KRT5 and HLA-J were
associated with high tumor regression grade status (Spearman Rho 0,5239; p = 0.0256
and Spearman Rho 0,5821; p = 0.0089). Kaplan Meier analysis revealed that increase
in HLA-J mRNA expression after NACT indicated worse progression free survival (p = 0,0096).
Conclusion HLA-J mRNA expression is thought to be associated with basal like features in breast
cancer and predicts therapy outcome after NACT. The dynamic differences in HLA-J expression
upon NACT demonstrating a counter reaction of tumor tissues to prevent elimination
by increased immune infiltration as induced by NACT. The counterreaction is associated
with worse prognosis. This is the first study identifying HLA-J as a new predictive
marker, which is involved in immune evasion.
