Understanding and targeting cancer using mass spectrometry

By Dr. Emma H. Doud

Although cancer death rates have dropped in the last 20 years, it is still the 2nd most common cause of death in the United States (Cancer Stat Facts, NCI) and a leading cause of death worldwide. Understanding the biological mechanisms which cause disease and therapeutic resistance is crucial for the creation of new treatments and improving survival rates. Some known mechanisms behind cancer progression include changes in the function or abundance of proteins. Proteins are present in every cell in our body and are responsible for many different functions such as helping to build and repair tissues, transporting molecules in and out of cells, and controlling chemical reactions in the body. Glycoproteins are proteins that have sugar or glycan molecules attached to them, and they play important roles in many biological processes, including cell signaling, immune response, and disease progression. Changes in the specific type and amount of the sugars on proteins have been linked to many cancers including breast, ovarian, lymphoma, colon, myeloma, pancreatic and prostate.

Mass spectrometers are state of the art analytical instruments which allow researchers to precisely measure the mass and abundance of small molecules, proteins and modified proteins in biological samples. In the review article “Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery” the authors discuss some of the mechanisms implicated in glycoprotein disruption and cancer progression, and how mass spectrometry can be used on different types of samples to answer various biological questions. Mass spectrometry-based glycoproteomic workflows provide a powerful tool for the identification and characterization of glycoproteins, and they have shown promise in cancer biomarker discovery.

The article discusses the different steps involved in mass spectrometry-based glycoproteomic workflows for cancer biomarker discovery (Figure 1). These steps can include glycoprotein enrichment, enzymatic digestion, mass spectrometry analysis, and data analysis. The authors also discuss the advantages and limitations of different techniques for glycoprotein enrichment and enzymatic digestion.

Figure 1. From the paper. Various sample preparation and technical workflows can all be useful in order to better understand how glycans are changed in different types of cancer.

One of the challenges in glycoproteomic analysis is the heterogeneity of glycosylation patterns on glycoproteins. This heterogeneity can complicate analysis and make it difficult to identify cancer specific glycan profiles. The authors suggest several strategies to address this challenge, including using complementary enrichment techniques and analyzing glycopeptides at the MS/MS level compared to known standards.

Another challenge in glycoproteomic analysis is the large amount of data generated by mass spectrometry analysis, and the current variance among available software for glycan and glycopeptide identification. The authors mention several current bioinformatics tools to analyze the data and identify potential biomarkers. They also discuss the importance of validation studies to confirm the identity and clinical relevance of potential biomarkers.

The identification of glycoproteins that are differentially expressed in cancer patients compared to healthy individuals may lead to the discovery of new cancer biomarkers that can be used for early detection, diagnosis, and targeted therapies. More widespread use of the several available mass spectrometry-based glycoproteomics workflows described here has the potential to revolutionize cancer diagnosis and treatment. While there are still challenges to overcome, the continued development and refinement of these workflows hold promise for improving cancer outcomes in the future.

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Article Details
Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery
Emma H. Doud, PhD and Elizabeth S. Yeh, PhD
First published online February 6, 2023
DOI: 10.1177/15330338221148811
Technology in Cancer Research & Treatment

About the Author

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Dr. Emma Doud is currently an Assistant Research Professor in the department of Biochemistry and Molecular Biology and the Associate Director of the Center for Proteome Analysis at Indiana University School of Medicine. She graduated with dual degrees in Chemistry and Biology from Purdue University. She went on to earn her PhD in Chemistry and Chemical Biology at Harvard University where she studied the genetics and biochemistry of moenomycin biosynthesis with Professors Dan Kahne and Suzanne Walker. She then worked at the Proteomics Center of Excellence at Northwestern University, with Dr. Neil Kelleher. Her current research focuses on utilizing state of the art proteomics technology to understand how proteostasis impacts human health and disease with a focus on protein abundance, post-translational modifications, protein-protein interactions, and stability.

Twitter Handle: @fireinlab