Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation ... View Full Text


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Article Info

DATE

2015-02-14

AUTHORS

Michela Bertuzzi, Cristina Marelli, Renzo Bagnati, Alessandro Colombi, Roberto Fanelli, Calogero Saieva, Marco Ceroti, Benedetta Bendinelli, Saverio Caini, Luisa Airoldi, Domenico Palli

ABSTRACT

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. More... »

PAGES

56

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-015-1058-7

DOI

http://dx.doi.org/10.1186/s12885-015-1058-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007051495

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25884309


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31 schema:description 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.
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39 C9
40 EPIC samples
41 European Prospective Investigation
42 Florence cohort
43 Florence-EPIC cohort
44 Prospective Investigation
45 Targeted proteomics
46 acetylmuramoyl
47 aim
48 alanine amidase
49 alpha-2-HS-glycoprotein
50 amidase
51 analysis
52 apolipoprotein C
53 association
54 biology tools
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56 cancer
57 cancer cases
58 cancer detection
59 cancer mortality world
60 cancer risk
61 candidate biomarkers
62 candidate pre-diagnosis marker
63 case-control study
64 cases
65 cause
66 chromatography-tandem mass spectrometry
67 clusterin
68 clusterin levels
69 cohort
70 colorectal cancer
71 colorectal cancer cases
72 colorectal cancer detection
73 colorectal cancer risk
74 complement C4-B
75 complement component C9
76 component C9
77 comprehensive plasma proteome analysis
78 control
79 detection
80 development
81 diagnosis
82 disease development
83 disease diagnosis
84 disease risk
85 evaluation
86 exploratory study
87 higher clusterin levels
88 identification
89 identification of people
90 immune response
91 increase
92 inflammation
93 intervention
94 investigation
95 levels
96 liquid chromatography-tandem mass spectrometry
97 logistic model
98 major cause
99 mannose-binding protein C
100 markers
101 mass spectrometry
102 men
103 model
104 mortality world
105 multivariate logistic model
106 nutrition
107 nutrition studies
108 people
109 phase 1
110 phase 2 study
111 phase 3
112 pilot study
113 plasma clusterin
114 plasma protein biomarkers
115 plasma proteins
116 plasma proteome analysis
117 plasma samples
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119 pre-diagnosis marker
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121 preliminary study
122 prevention
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126 protein
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133 response
134 results
135 risk
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137 samples
138 significant positive association
139 similar preliminary study
140 spectrometry
141 study
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143 systems biology tools
144 time
145 tool
146 unit increase
147 validation
148 world
149 years
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