In recent years, various omics technologies have been developed, and multi-omics research has become popular to obtain new findings by combining multiple omics analysis technologies. In our research center, we are also conducting comprehensive analysis of cancer using proteogenomics, which integrates genomics, proteomics, and informatics.
As the first example, I introduce the development of cancer liquid biopsy technology targeting mutant proteins in extracellular vesicles (EVs). We have previously reported several protein biomarkers that are significantly upregulated in EVs in the blood of cancer patients (Int J Cancer (2018);142:607)(Mol Cancer Res (2021);19:834)(Cancer Sci (2022);113: 3960), but the problem was that the cancer specificity was not perfect. In this study, we constructed an individualized protein sequence database by converting the results of whole exon sequencing of tissues into amino acid sequences for each patient, and successfully obtained a comprehensive mutant protein profile for each patient by integrating the database with LC/MS analysis. In fact, somatic mutant proteins were identified from bladder cancer tissues, EVs in tissue culture medium, and urinary EVs. Importantly, a series of mutant proteins in urine EVs showed quantitative correlation with cystoscopy results in absolute quantitative measurement over time, indicating that this could be a new liquid biopsy modality.
The second is the comprehensive identification of HLA-presenting antigens with somatic mutation sequences (neoantigens), by integrating the results of immunopeptidome analysis, which comprehensively identifies HLA-presenting antigens, and individual patient genome analysis, which enables direct determination of neoantigens as potential targets for cancer immunotherapy. In fact, 44,815 HLA class-I presenting antigen peptides were identified from 17 colorectal cancer tissue samples, and neoantigens containing mutated sequences such as KRAS-G12V and CPPED1-R228Q were successfully determined (Commun Biol (2022);5:831).
I would like to discuss the potential of proteogenomics analysis technology using the above examples.