MoCadb-logoMoCadb - Study ID Exp27492143c

PubMed ID27492143
AuthorsPeltier J(1), Roperch JP(2), Audebert S(3), Borg JP(3), Camoin L(4).
TitleQuantitative proteomic analysis exploring progression of colorectal cancer: Modulation of the serpin family.
JournalJ Proteomics. 2016 Oct 4;148:139-48.
AbstractColorectal cancer (CRC) remains a major cause of cancer related-death in developed countries. The mortality risk is correlated with the stage of CRC determined at the primary diagnosis and early diagnosis is associated with enhanced survival rate. Currently, only faecal occult blood tests are used to screen for CRC. Consequently, there is an incentive to identify specific markers of CRC. We used quantitative proteomic analysis of serum samples to characterize protein profiles in adenoma, CRC and healthy control samples. We identified 89 distinct proteins modulated between normal, colorectal adenoma and carcinoma patients. This list emphasizes proteins involved in enzyme regulator activities and in particular the serpin family. In serum samples, protein profiles of three members of the serpin family (SERPINA1, SERPINA3 and SERPINC1) were confirmed by ELISA assays. We obtained sensitivity/specificity values of 95%/95% for both SERPINA1 and SERPINC1, and 95%/55% for SERPINA3. This study supports the idea that serum proteins can discriminate adenoma and CRC patients from unaffected patients and reveals a panel of regulated proteins that might be useful for selecting patients for colonoscopy. By evaluating SERPINA1, SERPINA3 and SERPINC1, we highlight the potential role of the serpin family during the development and progression of CRC.SIGNIFICANCE: Colorectal cancer (CRC) remains a major cause of cancer mortality throughout the world. However, very few CRC biomarkers have satisfactory sensitivity and specificity in clinical practice. To the best of our knowledge our study is the first to profile sera proteomes between adenoma, CRC and healthy patients. We report a comprehensive list of proteins that may be used as early diagnostic biomarkers of CRC. It is noteworthy that 17% of these modulated proteins have been previously described as candidate biomarkers in CRC. Enzyme regulator activity was found to be the main molecular function among these proteins and, in particular, there was an enrichment of members of the serpin family. The subsequent verification on a new cohort by ELISA demonstrates that these serpins could be useful to discriminate healthy from colorectal carcinoma patients with a high sensitivity and specificity. The combination of these biomarkers should increase predictive powers of CRC diagnosis. The remaining candidates form a reserve for further evaluation of additional biomarkers for CRC diagnosis.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection methodSample
Homo sapiensbloodserumColorectal cancer (CRC)30LC-MS/MSDem27492143b, Dem27492143c

Sample description and preparation

N (case)15
N (control)15
Disease (case)Colorectal cancer (CRC)
Disease (control)Adenoma
Preparation specific methodiTRAQ-labelling
Storage condition-80C

Sample analysis

Software analysis toolProteinPilot v4.2.0
Software thresholdFDR<0.05

Molecule list

Molecule IDextExternal IDGeneNameSource accRegulation (case/control)Scores
A5625 A1AG1_HUMANORM1, AGP1, ORM2Alpha-1-acid glycoprotein 1 precursorORM1ratio: 11.07
A5625 A1AG1_HUMANORM1, AGP1, ORM2Alpha-1-acid glycoprotein 1 precursorORM2ratio: 2.07
A8369 A1AT_HUMANA1A, SERPINA1, AATAlpha-1-antitrypsin precursorSERPINA1ratio: 2.61
A735C A1BG_HUMANA1BGAlpha-1B-glycoprotein precursorA1BGratio: -2.21
A742C A2GL_HUMANLRG1, LRGLeucine-rich alpha-2-glycoprotein precursorLRG1ratio: 2.01
A8381 AACT_HUMANSERPINA3, AACT, GIG24Alpha-1-antichymotrypsin precursorSERPINA3ratio: 1.03
A4548 ACTB_HUMANACTB, PS1TP5BP1Actin, cytoplasmic 1ACTBratio: 1.46
A1924 ALDOB_HUMANALDOB, ALDBFructose-bisphosphate aldolase BALDOBratio: 4.09
A4566 ALS_HUMANIGFALS, ALSInsulin-like growth factor binding protein complex acid labile chain precursorIGFALSratio: -3.1
A8384 ANT3_HUMANAT3, SERPINC1, PRO0309Antithrombin-III precursorSERPINC1ratio: -1.06
A1552 APOA1_HUMANAPOA1, A175PApolipoprotein A-I precursorAPOA1ratio: -3.22
A1176 APOE_HUMANAPOEApolipoprotein E precursorAPOEratio: 1.28
A5947 BTD_HUMANBTDBiotinidase precursorBTDratio: -1.63
A5964 CAH2_HUMANCA2Carbonic anhydrase 2CA2ratio: -1.31
A6000 CBPB2_HUMANCPB2, PCPBCarboxypeptidase B2CPB2ratio: -1.36
A6053 CHLE_HUMANBCHE, CHE1Butyrylcholine esteraseBCHEratio: -2.42
A6086 CNDP1_HUMANCNDP1, CN1, CPGL2Beta-Ala-His dipeptidase precursorCNDP1ratio: -3.66
A1624 CO7_HUMANC7Complement component C7 precursorC7ratio: -2.94
A6355 DOPO_HUMANDBHDopamine beta-monooxygenase precursorDBHratio: -2.73
B4933 ELK1_HUMANELK1ETS-domain protein Elk-1CFPratio: -1.43
B5277 F110A_HUMANFAM110A, F10Protein C20orf55F10ratio: -2.15
A8774 FBLN3_HUMANEFEMP1, FBLN3, FBNLEGF-containing fibulin-like extracellular matrix protein 1 precursorEFEMP1ratio: -1.47
A9298 FCG3A_HUMANFCGR3A, CD16A, FCG3Low affinity immunoglobulin gamma Fc region receptor III-A precursorFCGR3Aratio: 2.33
A1739 FHR5_HUMANCFHR5, CFHL5, FHR5Complement factor H-related protein 5 precursorCFHR5ratio: 1.54
A1467 FIBA_HUMANFGAFibrinogen alpha/alpha-E chain precursorFGAratio: 2.78
A1466 FINC_HUMANFN1, FNFibronectinFN1ratio: -3.87
A1741 HBA_HUMANHBA1, HBA2, HBZHemoglobin subunit alphaHBA1ratio: 2.05
A1742 HBB_HUMANHBB, beta-globinHemoglobin beta chainHBBratio: 2.36
A5356 HORN_HUMANHRNR, S100A18HornerinHRNRratio: 4.83
A9356 IL1AP_HUMANIL1RAP, IL1R3Interleukin-1 receptor accessory protein precursorIL1RAPratio: -1.31
A3852 K22E_HUMANKRT2, KRT2A, KRT2EKeratin, type II cytoskeletal 2 epidermalKRT2ratio: -2.68
A8438 KAIN_HUMANSERPINA4, KST, PI4Kallistatin precursorSERPINA4ratio: -3.34
A1541 KLKB1_HUMANKLKB1, KLK3Plasma kallikrein precursorKLKB1ratio: -2.96
A1539 KNG1_HUMANKNG1, BDK, KNGKininogen-1KNG1ratio: 4.83
A6935 LYSC_HUMANLYZ, LZMLysozyme C precursorLYZratio: -1.68
A1537 PZP_HUMANPZP, CPAMD6Pregnancy zone protein precursorPZPratio: 1.89
A0035 RIMS1_HUMANRIMS1, RAB3IP2, RIM1Regulating synaptic membrane exocytosis protein 1RIMS1ratio: 3.91
A278E S10A7_HUMANS100A7, PSOR1, S100A7CProtein S100-A7S100 A7ratio: 2.03
A498C SEPP1_HUMANSEPP1, SELPSelenoprotein P precursorSEPP1ratio: -2.96
A596C TETN_HUMANCLEC3B, TNATetranectin precursorCLEC3Bratio: -2.56
A1470 TSP1_HUMANTHBS1, TSP, TSP1Thrombospondin 1 precursorTHBS1ratio: -1.46
A648C TTHY_HUMANTTR, PALB, TBPATransthyretin precursorTTRratio: 2.54
A1521 VWF_HUMANVWF, F8VWFVon Willebrand factor precursorVWFratio: 1.29
A195A ZA2G_HUMANAZGP1, ZAG, ZNGP1Zinc-alpha-2-glycoprotein precursorAZGP1ratio: 1.36
A8533 ZPI_HUMANSERPINA10, ZPI, UNQ707/PRO1358Protein Z-dependent protease inhibitor precursorSERPINA10ratio: -1.63
A1631 HPT_HUMANHPHaptoglobin precursorHPratio: 1.71
A549D IBP3_HUMANIGFBP3, IBP3Insulin-like growth factor binding protein 3 precursorIGFBP3ratio: -5.65
A1937 SEM4B_HUMANSEMA4B, SEMAC, UNQ749/PRO1480Semaphorin 4B precursorSEMA4Bratio: -10.37

Compile date 10-20-2017© .