Updated project metadata. Colorectal cancer (CRC) is currently the third leading cause of cancer related mortality in the world. U.S. Food and Drug Administration-approval circulating tumor markers, including carcinoembryonic antigen, carbohydrate antigen (CA) 19-9 and CA125, were used as prognostic biomarker of CRC that attributed to low sensitivity in diagnosis of CRC. Therefore, our purpose is to develop a novel strategy for novel clinical biomarker for early CRC diagnosis. We used mass spectrometry (MS) methods such as nanoLC-MS/MS, targeted LC-MS/MS, and stable iso-tope-labeled multiple reaction monitoring (MRM) MS coupled to machine learning algorithms and logistic regression to analyze plasma samples from patients with early-stage CRC, late-stage CRC, and healthy controls (HCs).