Increased expression of the immunoproteasome subunits PSMB8 and PSMB9 by cancer cells correlate with better outcomes for triple-negative breast cancers

Abstract

Proteasome dependency is a feature of many cancers that can be targeted by proteasome inhibitors. For some cancer types, notably breast cancer and triple-negative breast cancer (TNBC), high mRNA expression of a modified form of the proteasome, called the immunoproteasome (ImP), correlates with better outcomes and higher expression of one ImP subunit was associated with slower tumor growth in a small patient cohort. While these findings are in line with an anti-tumoral role of the ImP in breast cancer, studies investigating ImP expression at the protein level in large patient cohorts are lacking. Furthermore, while ImPs can be found in both immune and non-immune cells, the cellular source is often ignored in correlative studies. In order to determine the impact of ImP expression on breast cancer outcomes, we assessed the protein expression and cellular source of the ImP subunits PSMB8 and PSMB9 in a cohort of 2070 patients. Our data show a clear correlation between high ImP expression and better outcomes, most notably for TNBC patients and when tumor cells rather than stromal or immune cells express PSMB8 or PSMB9. Our results therefore suggest that ImP expression by tumor cells could be used as prognostic markers of TNBC outcomes.

Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes

“…A few genes and enriched categories are shared with Community Normal 392, but it does not share any interactions with LumA 111 and Her2 127 communities. This cluster presents genes for MHC class I molecules ( 54 ), as well as TAP1 and TAP2 molecules ( 55 ), together with PSMB8 and PSMB9 members of the immunoproteasome, which help in the process of antigen cross-presentation ( 56 , 57 ). Enrichment classes shared by this cluster share the theme of antigen processing and presentation and the antigen-presenting side of cytotoxic T-cell action ( 54 ).…”

Single-cell RNA sequencing combined with mendelian randomization analysis identifies putatively causal genes associated with Gastric cancer

“…The role of PSMB9 is not the same in different tumors, which indicates different types of tumors contain different tumor environments. For example, higher expression of PSMB9 tend to have better prognosis in breast invasive carcinoma (BRCA) 19 , ovarian serous cystadenocarcinoma (OV) 20 , and non-small cell lung cancer (NSCLC) 21 . However, higher expression of PSMB9 showed worse prognosis in lower-grade glioma (LGG) 22 .…”

DataSheet_3.pdf

“…A few genes and enriched categories are shared with Community Normal 392, but it does not share any interactions with LumA 111 and Her2 127 communities. This cluster presents genes for MHC class I molecules (54), as well as TAP1 and TAP2 molecules (55), together with PSMB8 and PSMB9 members of the immunoproteasome, which help in the process of antigen crosspresentation (56,57). Enrichment classes shared by this cluster share the theme of antigen processing and presentation and the antigen-presenting side of cytotoxic T-cell action (54).…”