The first diagnostic biomarkers to be used for cancer testing and screening were primarily proteins such as alpha-fetoprotein (AFP) and prostate-specific antigen (PSA), which were discovered and developed for clinical application in the early stages of biomedical research. With the advances of biotechnology, biomarker research has been transformed and advanced to include circulating tumoral DNA such as mutated EGFR gene , various types of RNA, particularly microRNA , genes released during genetic modification and cell division , peptides and proteins including hormones, receptors, antibodies , also lipids and other metabolites , circulating tumor cells , and extracellular vesicles such as exosomes .