Abstract
Neoantigen-based immunotherapy has yielded promising results in clinical trials. However, it is limited to tumor-specific mutations, and is often tailored to individual patients. Identifying suitable tumor-specific antigens is still a major challenge. Previous proteogenomics studies have identified peptides encoded by predicted non-coding sequences in human genome. To investigate whether tumors express specific peptides encoded by non-coding genes, we analyzed published proteomics data from five cancer types including 933 tumor samples and 275 matched normal samples and compared these to data from 31 different healthy human tissues. Our results reveal that many predicted non-coding genes such as DGCR9 and RHOXF1P3 encode peptides that are overexpressed in tumors compared to normal controls. Furthermore, from the non-coding genes-encoded peptides specifically detected in cancers, we predict a large number of “dark antigens” (neoantigens from non-coding genomic regions), which may provide an alternative source of neoantigens beyond standard tumor specific mutations.
Highlights
Neoantigen-based immunotherapy has yielded promising results in clinical trials
In addition to RNA level detection of pseudogene expression, several independent proteomics studies have identified peptide evidence of pseudogene and long noncoding RNAs (lncRNAs) translation in normal tissues and cancer cell lines[1,2,3]. It has not been systematically investigated if predicted noncoding genes encode peptides that can be found in tumor tissues or whether translation of noncoding genes is a sporadic event, or if it is regulated in different types of tumors
We downloaded proteomics data collected from 40 normal samples from 31 healthy tissues, 933 tumor samples, and 275 tumor-adjacent normal samples from the PRoteomics IDEntifcations (PRIDE) database and National Cancer Institute Clinical Proteomic Tumor Analysis Consortium (CPTAC) Data Portal[11,12]
Summary
Neoantigen-based immunotherapy has yielded promising results in clinical trials. it is limited to tumor-specific mutations, and is often tailored to individual patients. To investigate whether tumors express specific peptides encoded by non-coding genes, we analyzed published proteomics data from five cancer types including 933 tumor samples and 275 matched normal samples and compared these to data from 31 different healthy human tissues. In addition to RNA level detection of pseudogene expression, several independent proteomics studies have identified peptide evidence of pseudogene and lncRNA translation in normal tissues and cancer cell lines[1,2,3] It has not been systematically investigated if predicted noncoding genes encode peptides that can be found in tumor tissues or whether translation of noncoding genes is a sporadic event, or if it is regulated in different types of tumors. Our second goal was to investigate whether these non-coding region-encoded peptides have any predicted affinity with MHC class I molecules as potential new cancer neoantigens
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