Identification of Deregulated Proteins in Mutated / Breast and Ovarian Cancers for Vectorized Biologics.

Administration of PARP inhibitors against breast and ovarian cancers with BRCA1 and BRCA2 mutations has shown clinical benefits in patients. However, these agents are also toxic and have a narrow therapeutic index. In this work, we aimed to identify membrane proteins that are specifically upregulated in these cancers. We interrogated public datasets to analyze genes upregulated or downregulated when these mutations were present, compared with wild-type cancers. Surface protein expression and functional annotation analyses were also performed. In breast cancer, we identified 11 upregulated and 44 downregulated transcripts in BRCA1-mut, while 10 upregulated and 57 downregulated transcripts were identified in BRCA2-mut cancers. In ovarian cancer, 79 transcripts were upregulated and 123 were downregulated in BRCA1-mut cancers, while five were upregulated and seven were downregulated in BRCA2-mut tumors. Regarding the biological function related to these genes, in BRCA1-mutated ovarian cancers, the main functions of upregulated genes included MHC assembly or regulation of the interferon gamma pathway; in BRCA2-mut ovarian cancers, regulation of phosphorylation and signaling; in BRCA1-mut breast cancers, cell damage repair and angiogenesis; and finally, in BRCA2-mut breast cancers, cytokine production and T-cell migration. Genes expressed in the surface membrane or extracellular matrix and related to patient outcomes included B3GNT7 and CTSV in BRCA2-mut breast cancers, exhibiting detrimental prognoses. CD6, CXCL9, and CXCL13 were associated with favorable outcomes in BRCA1-mutant ovarian cancers. The last three genes were also correlated with the infiltration of effector T cells and dendritic cells in ovarian tumors. In summary, we identified deregulated candidate genes that could be used as therapeutic targets.