[en] Abstract
Background: Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the
identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for
reducing CRC incidence and increasing patient’s survival.
Methods: We analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by
label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohisto‑
chemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages.
Results: Out of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among
groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed differ‑
ent expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues.
Conclusion: We highlighted three proteins that require further investigations to better characterise their role in early
CRC carcinogenesis and their potential as early CRC markers.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
MASSOT, Charlotte ; Centre Hospitalier Universitaire de Liège - CHU > GIGA-R > Hépato-gastroentérologie et oncologie digestive -gastroentérologie translationnelle
Bertrand, Virginie ; Université de Liège > Département de chimie (sciences) > Département de chimie (sciences)
Longuespée, Rémi ; Université de Liège > Département de chimie (sciences) > Center for Analytical Research and Technology (CART)
BLETARD, Noëlla ; Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques
SOMJA, Joan ; Centre Hospitalier Universitaire de Liège - CHU > Service dermatopathologie
Mazzucchelli, Gabriel ; Université de Liège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Smargiasso, Nicolas ; Université de Liège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
De Pauw-Gillet, Marie-Claire ; Université de Liège > Département des sciences biomédicales et précliniques > Histologie - Cytologie
Delvenne, Philippe ; Université de Liège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
MALAISE, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Service de rhumatologie
COIMBRA MARQUES, Carla ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdo, sénologique, endocrine et de transplantation
POLUS, Marc ; Centre Hospitalier Universitaire de Liège - CHU > Service de gastroentérologie, hépatologie, onco. digestive
De Pauw, Edwin ; Université de Liège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
MEUWIS, Marie-Alice ; Centre Hospitalier Universitaire de Liège - CHU > GIGA-R > Service d'hépato-gastroentérologie et oncologie digestive/ Gastroenterologie Translationnelle
Louis, Edouard ; Université de Liège > Département des sciences cliniques > Hépato-gastroentérologie
Peters U, Bien S, Zubair N. Genetic architecture of colorectal cancer. Gut. 2015;64:1623–36.
Allen JI. Quality measures for colonoscopy: where should we be in 2015? Curr Gastroenterol Rep. 2015;17:10.
Hassan C, Giorgi Rossi P, Camilloni L, Rex DK, Jimenez-Cendales B, Ferroni E, Borgia P, Zullo A, Guasticchi G. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther. 2012;36:929–40.
Langan RC, Mullinax JE, Raiji MT, Upham T, Summers T, Stojadinovic A, Avital I. Colorectal cancer biomarkers and the potential role of cancer stem cells. J Cancer. 2013;4:241–50.
Labianca R, Nordlinger B, Beretta GD, Brouquet A, Cervantes A, ESMO Guidelines Working Group. Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol. 2010;21(Suppl. 5):v70–7.
Balmana J, Castells A, Cervantes A. Familial colorectal cancer risk: ESMO clinical practice guidelines. Ann Oncol. 2010;21(Suppl. 5):v78–81.
Glimelius B, Pahlman L, Cervantes A. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl. 5):v82–6.
Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47:251–5.
Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. 6th ed. Edinburg: Churchill Livingstone; 2007.
Marée R, Stévens B, Rollus L, Rocks N, Lopez XM, Salmon I, Cataldo D, Wehenkel L. A rich internet application for remote visualization and collaborative annotation of digital slides in histology and cytology. Diagn Pathol. 2013;8:4.
Quesada-Calvo F, Bertrand V, Longuespée R, Delga A, Mazzucchelli G, Smargiasso N, Baiwir D, Delvenne P, Malaise M, De Pauw-Gillet M-C, et al. Comparison of two FFPE preparation methods using label-free shotgun proteomics: application to tissues of diverticulitis patients. J Proteomics. 2015;112:250–61.
Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, et al. The human colon cancer methylome shows similar hypo-and hyper-methylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41:178–86.
Lin G, He X, Ji H, Shi L, Davis RW, Zhong S. Reproducibility probability score—incorporating measurement variability across laboratories for gene selection. Nat Biotechnol. 2006;24:1476–7.
Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19:185–93.
Vizcaino JA, Cote RG, Csordas A, Dianes JA, Fabregat A, Foster JM, Griss J, Alpi E, Birim M, Contell J, et al. The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013. Nucleic Acids Res. 2013;41:D1063–9.
Vissers JP, Langridge JI, Aerts JM. Analysis and quantification of diagnostic serum markers and protein signatures for Gaucher disease. Mol Cell Proteomics. 2007;6:755–66.
Roblick UJ, Hirschberg D, Habermann JK, Palmberg C, Becker S, Kruger S, Gustafsson M, Bruch HP, Franzen B, Ried T, et al. Sequential proteome alterations during genesis and progression of colon cancer. Cell Mol Life Sci. 2004;61:1246–55.
Jimenez CR, Knol JC, Meijer GA, Fijneman RJ. Proteomics of colorectal cancer: overview of discovery studies and identification of commonly identified cancer-associated proteins and candidate CRC serum markers. J Proteomics. 2010;73:1873–95.
Albrethsen J, Knol JC, Piersma SR, Pham TV, de Wit M, Mongera S, Carvalho B, Verheul HM, Fijneman RJ, Meijer GA, Jimenez CR. Subnuclear proteomics in colorectal cancer: identification of proteins enriched in the nuclear matrix fraction and regulation in adenoma to carcinoma progression. Mol Cell Proteomics. 2010;9:988–1005.
Wisniewski JR, Dus-Szachniewicz K, Ostasiewicz P, Ziolkowski P, Rakus D, Mann M. Absolute proteome analysis of colorectal mucosa, adenoma, and cancer reveals drastic changes in fatty acid metabolism and plasma membrane transporters. J Proteome Res. 2015;14:4005–18.
Mu Y, Chen Y, Zhang G, Zhan X, Li Y, Liu T, Li G, Li M, Xiao Z, Gong X, Chen Z. Identification of stromal differentially expressed proteins in the colon carcinoma by quantitative proteomics. Electrophoresis. 2013;34:1679–92.
Quesada-Calvo F, Bertrand V, Longuespee R, Delga A, Mazzucchelli G, Smargiasso N, Baiwir D, Delvenne P, Malaise M, De Pauw-Gillet MC, et al. Comparison of two FFPE preparation methods using label-free shotgun proteomics: application to tissues of diverticulitis patients. J Proteomics. 2014;112C:250–61.
Trudgian DC, Ridlova G, Fischer R, Mackeen MM, Ternette N, Acuto O, Kessler BM, Thomas B. Comparative evaluation of label-free SINQ normalized spectral index quantitation in the central proteomics facilities pipeline. Proteomics. 2011;11:2790–7.
Mann M, Kulak NA, Nagaraj N, Cox J. The coming age of complete, accurate, and ubiquitous proteomes. Mol Cell. 2013;49:583–90.
Richardson K, Denny R, Hughes C, Skilling J, Sikora J, Dadlez M, Manteca A, Jung HR, Jensen ON, Redeker V, et al. A probabilistic framework for peptide and protein quantification from data-dependent and dataindependent LC–MS proteomics experiments. OMICS. 2012;16:468–82.
Geromanos SJ, Vissers JP, Silva JC, Dorschel CA, Li GZ, Gorenstein MV, Bateman RH, Langridge JI. The detection, correlation, and comparison of peptide precursor and product ions from data independent LC–MS with data dependant LC–MS/MS. Proteomics. 2009;9:1683–95.
Luebker SA, Wojtkiewicz M, Koepsell SA. Two methods for proteomic analysis of formalin-fixed, paraffin embedded tissue result in differential protein identification, data quality, and cost. Proteomics. 2015;15:3744–53.
Tanca A, Pagnozzi D, Burrai GP, Polinas M, Uzzau S, Antuofermo E, Addis MF. Comparability of differential proteomics data generated from paired archival fresh-frozen and formalin-fixed samples by GeLC–MS/MS and spectral counting. J Proteomics. 2012;77:561–76.
Jang BG, Kim HS, Kim KJ, Rhee YY, Kim WH, Kang GH. Distribution of intestinal stem cell markers in colorectal precancerous lesions. Histopathology. 2015;68(4):567–77.
van der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology. 2009;137:15–7.
Zhang J, Liu WL, Tang DC, Chen L, Wang M, Pack SD, Zhuang Z, Rodgers GP. Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development. Gene. 2002;283:83–93.
Liu BG, Cao YB, Cao YY, Zhang JD, An MM, Wang Y, Gao PH, Yan L, Xu Y, Jiang YY. Altered protein profile of lymphocytes in an antigenspecific model of colitis: a comparative proteomic study. Inflamm Res. 2007;56:377–84.
Oue N, Sentani K, Noguchi T, Ohara S, Sakamoto N, Hayashi T, Anami K, Motoshita J, Ito M, Tanaka S, et al. Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. Int J Cancer. 2009;125:2383–92.
Clemmensen SN, Glenthoj AJ, Heeboll S, Nielsen HJ, Koch C, Borregaard N. Plasma levels of OLFM4 in normals and patients with gastrointestinal cancer. J Cell Mol Med. 2015;19(12):2865–73. doi:10.1111/jcmm.12679.
Sharpe LJ, Luu W, Brown AJ. Akt phosphorylates Sec24: new clues into the regulation of ER-to-Golgi trafficking. Traffic. 2011;12:19–27.
Seko N, Oue N, Noguchi T, Sentani K, Sakamoto N, Hinoi T, Okajima M, Yasui W. Olfactomedin 4 (GW112, hGC-1) is an independent prognostic marker for survival in patients with colorectal cancer. Exp Ther Med. 2010;1:73–8.
Besson D, Pavageau AH, Valo I, Bourreau A, Belanger A, Eymerit-Morin C, Mouliere A, Chassevent A, Boisdron-Celle M, Morel A, et al. A quantitative proteomic approach of the different stages of colorectal cancer establishes OLFM4 as a new nonmetastatic tumor marker. Mol Cell Proteomics. 2011;10(M111):009712.
Roy HK, Olusola BF, Clemens DL, Karolski WJ, Ratashak A, Lynch HT, Smyrk TC. AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis. 2002;23:201–5.
Wang J, Wang X, Lin S, Chen C, Wang C, Ma Q, Jiang B. Identification of kininogen-1 as a serum biomarker for the early detection of advanced colorectal adenoma and colorectal cancer. PLoS ONE. 2013;8:e70519.
Navaneethan U, Lourdusamy V, Gk Venkatesh P, Willard B, Sanaka MR, Parsi MA. Bile proteomics for differentiation of malignant from benign biliary strictures: a pilot study. Gastroenterol Rep. 2015;3:136–43.
Liu W, Liu B, Cai Q, Li J, Chen X, Zhu Z. Proteomic identification of serum biomarkers for gastric cancer using multi-dimensional liquid chromatography and 2D differential gel electrophoresis. Clin Chim Acta. 2012;413:1098–106.
Abdullah-Soheimi SS, Lim BK, Hashim OH, Shuib AS. Patients with ovarian carcinoma excrete different altered levels of urine CD59, kininogen-1 and fragments of inter-alpha-trypsin inhibitor heavy chain H4 and albumin. Proteome Sci. 2010;8:58.
Mu AK, Lim BK, Hashim OH, Shuib AS. Identification of O-glycosylated proteins that are aberrantly excreted in the urine of patients with early stage ovarian cancer. Int J Mol Sci. 2013;14:7923–31.
Abdul-Rahman PS, Lim BK, Hashim OH. Expression of high-abundance proteins in sera of patients with endometrial and cervical cancers: analysis using 2-DE with silver staining and lectin detection methods. Electrophoresis. 2007;28:1989–96.
