The sensitivity and specificity of serum glycan-based biomarkers for cancer detection

Most of clinically used serum biomarkers for cancer detection were established in early 1980s when the Nobel Prize in physiology or medicine was awarded for the "discovery of the principle for the production of monoclonal antibodies." Using this "Nobel" technology, various monoclonal antibodies were obtained when different types of cancer cells were injected into mice and the ligands on the cancer cell surface were characterized. Both aberrant glycan structures and aberrant glycan-associated glycoproteins were revealed as a common feature of cancer cell surfaces through the specific interactions with the monoclonal antibodies. These results indicate that the biosynthesis of the environment-sensitive glycan structures goes awry in cancer cells, which is beyond genetic mutations. Later on, the glycan-related biomarkers were detected in the sera of cancer patients and then developed into serum biomarkers, such as CA125, CA153, CA195, CA199, CA242, CA27.29, CA50, and CA724, which are still in clinical use as of today. During the past 30 years, even with the advancement of different OMICS technologies not limited to genomics, epigenomics, proteomics, glycomics, lipidomics, and metabolomics, very few serum biomarkers have been introduced into clinical practice. The reason is that most of the newly discovered cancer biomarkers are inferior in terms of sensitivity and specificity to these biomarkers. We will summarize the reported sensitivity and specificity of currently used cancer biomarkers, especially the glycan-related biomarkers, in the forms of tables and radar plots and discuss the pros and cons of currently used cancer biomarkers.