1. a b c d 30% AcN 30% Organic (143 Features) FT 200 500 1000 #Features25 18 43 43 CV0.2 0.3 0.3 0.5 R 2 0.99 0.98 0.96 1.0 45% Organic (237 Features) FT 200 500 1000 #Features52 56 62 67 CV0.2 0.2 0.2 0.3 R 2 0.98 0.99 0.98 0.99 80% Organic (258 Features) FT 200 500 1000 #Features49 73 68 63 CV0.4 0.2 0.3 0.3 R 2 0.99 0.99 0.97 0.91 Method Supplemental Figure 1.

2. Pooled Serum 1) IgY-R7 Depletion Column 2) SPE w/Peptide Mactrotraps (C18/ SCX) 3) C4-RP HPLC (LC-MALDI-Spotter) 4) LC-MALDI-TOF-MS (isolate key fractions) 5) 1D-PAGE (In-gel tryptic digestion) 6) nLC-MS2 Validation by Western Blot Feature Increased in Kras vs. Control 6,560 6,620 m/z 2,000 1,500 500 0 Intensity C. Ras 6,568, m/z 100 50 0 Rel. Intensity 300 1,200 m/z MS2 Sequence Protein ID a. b. c. Supplemental Figure 2.

3. Extracellular Membrane Cytoplasm Nuclear Significant Hit Receptor Ligand Transcripton Factor Generic Protein Binding Protein Transporter Receptor Generic Enzyme Protease Kinase Legend Supplemental Figure 3.