HLA-J as a new predictive marker in breast cancer for neoadjuvant chemotherapy

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.

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Publication History

Article published online:
07 October 2020