Research

Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

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Abstract

Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic. Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature of transcriptional and translation regulatory mechanisms and the disparities between genomic and proteomic data from the same samples. In this study, we have examined tumor antigens as potential biomarkers for breast cancer using genomics and proteomics data from previously reported laser capture microdissected ER+ tumor samples. Results: We applied proteogenomic analyses to study the genetic aberrations of 32 tumor antigens determined in the proteomic data. We found that tumor antigens that are aberrantly expressed at the genetic level and expressed at the protein level, are likely involved in perturbing pathways directly linked to the hallmarks of cancer. The results found by proteogenomic analysis of the 32 tumor antigens studied here, capture largely the same pathway irregularities as those elucidated from large-scale screening of genomics analyses, where several thousands of genes are often found to be perturbed. Conclusion: Tumor antigens are a group of proteins recognized by the cells of the immune system. Specifically, they are recognized in tumor cells where they are present in larger than usual amounts, or are physiochemically altered to a degree at which they no longer resemble native human proteins. This proteogenomic analysis of 32 tumor antigens suggests that tumor antigens have the potential to be highly specific biomarkers for different cancers.

Primates Mammalia Vertebrata Chordata Animalia (Animals Chordates Humans Mammals Primates Vertebrates) - Hominidae [86215] human common female estrogen receptor mRNA expression tumor antigens expression proteogenomic biomarker 03502 Genetics - General 03508 Genetics - Human 10062 Biochemistry studies - Nucleic acids purines and pyrimidines 10064 Biochemistry studies - Proteins peptides and amino acids 16506 Reproductive system - Pathology 18506 Integumentary system - Pathology 24003 Neoplasms - Immunology 24004 Neoplasms - Pathology clinical aspects and systemic effects 34502 Immunology - General and methods 34508 Immunology - Immunopathology tissue immunology Dermatology Gynecology Molecular Genetics Oncology breast cancer Breast Neoplasms (MeSH) neoplastic disease reproductive system disease/female invasive ductal carcinoma neoplastic disease integumentary system disease genetic aberration genomics data proteomics data Biochemistry and Molecular Biophysics Human Medicine Medical Sciences immune system immune system laser capture microdissection laboratory techniques histology and cytology techniques GENETICS HUMAN BREAST-CANCER EPITHELIAL OVARIAN-CANCER SET ENRICHMENT ANALYSIS PHOSPHOGLYCERATE KINASE EXPRESSION PROFILES IMMUNE SURVEILLANCE SUPPRESSOR-CELLS CLINICAL-TRIALS TESTIS ANTIGEN BETA-CATENIN