Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer

Abstract

During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein–protein interaction, and pharmacogenomics data, are indispensable to glean into the cancer genome and proteome and these approaches have generated multidimensional universal studies of genes and proteins (OMICS) data which has the potential to facilitate precision medicine. However, due to slow progress in computational technologies, the translation of big omics data into their clinical aspects have been slow. In this review, attempts have been made to describe the role of high-throughput genomic and proteomic technologies in identifying a panel of biomarkers which could be used for the early diagnosis and prognosis of cancer.

Origins and clinical relevance of proteoforms in pediatric malignancies

“…Posttranslational modifications are capable of generating a functional change in the protein that can affect localization, abundance, catalytic activity, protein-protein interactions, and overall aberrant cell signaling [73]. Aberrant post-translational modification of some oncogenic proteins results in tumor initiation and are therefore increasingly recognized as potential targets for anti-cancer drugs [74]. In normal cells, the formation of PTMs is typically tightly controlled and often act as signals to trigger or terminate downstream regulatory processes.…”

Connecting Proteomics to Next‐Generation Sequencing: Proteogenomics and Its Current Applications in Biology

“…Proteogenomics has improved our understanding of cancer progression and metastasis. Importantly, it can also assist the discovery of biomarkers that enable cancers to be diagnosed at an early stage; or biomarkers of chemoresistance . By analyzing laser capture microdissected ER+ breast tumors on 32 previously identified tumor antigens, Olsen et al.…”

Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics

“…Today, biomarker research has been transformed by the fields of genomics, proteomics, metabolomics, and lipidomics. As a result, the possible molecular nature of a biomarker today is as varied as there are substances in the body, and includes circulating tumoral DNA (e.g., mutated EGFR gene [ 7 ] ), the various types of RNA (particularly microRNA [ 8 ] ), peptides and proteins (e.g., hormones, receptors, antibodies), [ 9 ] lipids and other metabolites, [ 10 ] circulating tumor cells, and non‐cellular vesicles called “exosomes”. [ 11 ] There are currently great expectations (e.g., [ 12–15 ] ) that these molecular and cellular biomarkers will provide the needed specificity, sensitivity, reproducibility, and cost‐effectiveness for the early diagnosis of particular types of cancer.…”