From Chemistry to Translational Medicine: The Application of Proteomics to Cancer Biomarker Discovery and Diagnosis

Abstract The study of complex protein mixtures and their interactions in cells and tissues has been difficult due to the tedious process involved in their characterization and analysis. The recent emergence of fast‐evolving and state‐of‐the‐art proteomics methodologies has provided a rapid and scalable platform for understanding the comprehensive proteome profiles from complex whole tissues or cells of various biological sources. Therefore, proteomics has been increasingly valuable to examine real‐time changes in protein expression of various tissues or body fluids from patients with various diseases, especially cancer, resulting in the identification of clinically useful biomarkers for diagnosis, prognosis and disease staging. In this review, we focus on potential biomarkers for (1) Helicobacter pylori‐associated gastric cancer, (2) hepatocellular carcinoma (HCC), and (3) renal cell carcinoma (RCC). In addition to the conventional gel‐based proteomics (1‐D or 2‐D gels), we have utilized a more advanced proteomic approach by incorporating stable isotope dimethyl labelling and shotgun proteomics strategy in combination with nanoliquid chromatography and tandem mass spectrometry (nanoLC‐MS/MS) to better characterize the biomarkers in several cancer tissues. By establishing a high‐throughput proteomics platform based on multiple reaction monitoring (MRM), we have successfully detected and analyzed potential protein markers at low concentrations in various normal and tumor tissues. This platform not only highlights the utility of proteomics for biomarker discovery but also can be uniquely applied to disease‐oriented translational medicine for diagnosis of diverse types of cancers and other diseases.