Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition: a pilot study

BMC Cancer

Domenico Palli²  Luisa Airoldi¹  Saverio Caini²  Benedetta Bendinelli²  Marco Ceroti²  Calogero Saieva²  Roberto Fanelli¹  Alessandro Colombi¹  Renzo Bagnati¹  Cristina Marelli¹  Michela Bertuzzi¹ 

[1]Department of Environmental Health Sciences, IRCCS–Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, Milano, 20156, Italy

[2]Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy

关键词: Mass spectrometry;    Proteomics;    Prospective study;    Colorectal cancer;    Early plasma biomarkers;   

Others  :  1134533
DOI  :  10.1186/s12885-015-1058-7

 received in 2014-11-12, accepted in 2015-01-29,  发布年份 2015

【 摘 要 】

Background

Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis.

Methods

After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case–control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed.

Results

Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann–Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein’s unit increase, but only in men.

Conclusions

The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.

【 授权许可】

   
2015 Bertuzzi et al.; licensee BioMed Central.

【 图 表 】

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