Dynamic changes of HLA-J expression during neoadjuvant treatment in ovarian cancer

Introduction The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. Especially the non-classical HLAs e.g. HLA-G are known for their high immunosuppressive effect and their potential as predictive marker in ovarian cancer. HLA-J, an HLA pseudogene shares the same immunosuppressive interaction sites as the non-classical HLAs and has an additional unique protein pattern. However, nothing is known about the pseudogene HLA-J and its possible immunological, prognostic and predictive features in ovarian cancer.

Material and Methods HLA-J expression was analysed in 35 ovarian cancer biopsies and its corresponding restates obtained from patients (FIGO stage III-IV) treated with neoadjuvant chemotherapy (NACT). mRNA was extracted from fresh frozen tissue and analysed with HLA-J gene specific TaqMan-based RT-qPCR, normalised to Calmodulin2 and calculated on basis of 40-DCT.

Results All ovarian cancer samples did express HLA-J and 14 out of 26 of matched sample pairs showed a substantial HLA-J upregulation after chemotherapy. Patients with had a high increase in HLA-J mRNA expression in samples from pre- to post NACT (40-DCT value ≥ 3; 8-fold change) had significant worse progression free survival (p-value = 0,0165) and overall survival (p-value = 0,0141).

Conclusion The falsely classified “pseudogene” HLA-J is overexpressed in ovarian cancer and frequently increased after NACT. Its extreme upregulation after NACT is consistently associated with resistance to chemotherapy as well as reduced progression free as well as overall survival. This is the first study identifying HLA-J as a new prognostic marker with possible immune suppressive effects.

Publikationsverlauf

Artikel online veröffentlicht:
07. Oktober 2020