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Research Article

Early Detection of Ovarian Cancer in Samples Pre-Diagnosis Using CA125 and MALDI-MS Peaks

JOHN F. TIMMS, USHA MENON, DMITRY DEVETYAROV, ALI TISS, STEPHANE CAMUZEAUX, KATHERINE MCCURRIE, ILIA NOURETDINOV, BRIAN BURFORD, CELIA SMITH, ALEKSANDRA GENTRY-MAHARAJ, RACHEL HALLETT, JEREMY FORD, ZHIYUAN LUO, VOLODYA VOVK, ALEX GAMMERMAN, RAINER CRAMER and IAN JACOBS
Cancer Genomics & Proteomics November 2011, 8 (6) 289-305;
JOHN F. TIMMS
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  • For correspondence: jtimms{at}wibr.ucl.ac.uk
USHA MENON
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DMITRY DEVETYAROV
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ALI TISS
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STEPHANE CAMUZEAUX
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KATHERINE MCCURRIE
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ILIA NOURETDINOV
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BRIAN BURFORD
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CELIA SMITH
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ALEKSANDRA GENTRY-MAHARAJ
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RACHEL HALLETT
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JEREMY FORD
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ZHIYUAN LUO
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VOLODYA VOVK
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ALEX GAMMERMAN
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RAINER CRAMER
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IAN JACOBS
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    Figure 1.
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    Figure 1.

    A: Processed full-mass range MS spectra for example case (red) and healthy control (green) samples. The spectra are averaged from 10 replicate acquisitions per sample. Peak 2 (m/z 7772) and peak 3 (m/z 9297) are indicated by arrows. B: Processed MS data for peak 2 (m/z 7772) and peak 3 (m/z 9297) plotted for all samples. Red is controls, blue is cases. C: MALDI MS spectrum of one of the fractions in which peak 3, identified as connective tissue-activating peptide III (CTAPIII), was eluted. The arrow indicates peak 3. D: Overlay of the spectrum in Figure S1A with randomly selected raw MALDI MS profiles from UKCTOCS serum analysis. E: ESI MS spectrum of the same sample used for the analysis that generated the spectrum shown in Figure 1C. F: m/z 1325-1333 region of the spectrum shown in Figure 1E. Single but not double oxidation is clearly visible, in agreement with CTAPIII possessing a single methionine residue.

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    Figure 2.

    A: Comparison of rules log C and log C – 2 log I(2) for peak 2 on time/case scale. B: Comparison of rules log C and log C – log I(3) for peak 3 on time/case scale. A circle means that a triplet was correctly classified by both rules. A cross means misclassification in both cases. A triangle upwards shows improvement and downwards shows deterioration after addition of the – log I(p) component. The figures demonstrate that most samples where addition of a peak to CA125 is beneficial (marked as upward triangles) are in the interval of 13-16 months before the diagnosis (dashed vertical lines).

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    Figure 3.

    A: Median dynamics of rules log C and log C – 2 log I(2) for cases only. B: Median dynamics of rules log C and log C – log I(3) for cases only.

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    Figure 4.

    A: Scatter dot plots for serum levels of platelet factor 4 (PF4) measured by ELISA for cases and matched controls in groups with different times to diagnosis. The horizontal bars indicate mean values. Significant changes between case groups are indicated. B: Continuous time to diagnosis data plotted for CA125. LOWESS curve fitting was applied to the CA125 data (solid lines) C: Continuous time to diagnosis data plotted for PF4. D: PF4 and CA125 data were plotted against one another (for cases only). Linear regression curve fitting was applied to the PF4/CA125 plot (dashed line).

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    Table III.
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  • Table IV.
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Cancer Genomics & Proteomics
Vol. 8, Issue 6
November-December 2011
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Early Detection of Ovarian Cancer in Samples Pre-Diagnosis Using CA125 and MALDI-MS Peaks
JOHN F. TIMMS, USHA MENON, DMITRY DEVETYAROV, ALI TISS, STEPHANE CAMUZEAUX, KATHERINE MCCURRIE, ILIA NOURETDINOV, BRIAN BURFORD, CELIA SMITH, ALEKSANDRA GENTRY-MAHARAJ, RACHEL HALLETT, JEREMY FORD, ZHIYUAN LUO, VOLODYA VOVK, ALEX GAMMERMAN, RAINER CRAMER, IAN JACOBS
Cancer Genomics & Proteomics Nov 2011, 8 (6) 289-305;

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Early Detection of Ovarian Cancer in Samples Pre-Diagnosis Using CA125 and MALDI-MS Peaks
JOHN F. TIMMS, USHA MENON, DMITRY DEVETYAROV, ALI TISS, STEPHANE CAMUZEAUX, KATHERINE MCCURRIE, ILIA NOURETDINOV, BRIAN BURFORD, CELIA SMITH, ALEKSANDRA GENTRY-MAHARAJ, RACHEL HALLETT, JEREMY FORD, ZHIYUAN LUO, VOLODYA VOVK, ALEX GAMMERMAN, RAINER CRAMER, IAN JACOBS
Cancer Genomics & Proteomics Nov 2011, 8 (6) 289-305;
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