Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification - PubMed (original) (raw)

Comparative Study

. 2012 May 4;11(5):2904-11.

doi: 10.1021/pr2012736. Epub 2012 Apr 4.

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Comparative Study

Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification

Katie Partyka et al. J Proteome Res. 2012.

Abstract

Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to investigate the clinical applicability of cyst fluid research obtained using surgical specimens. Matched pairs of operating-room collected (OR) and EUS-FNA samples from 12 patients were evaluated for the levels of three previously described biomarkers, CA 19-9, CEA, and glycan levels detected by wheat germ agglutinin on MUC5AC (MUC5AC-WGA). CA 19-9 and MUC5AC-WGA correlated well between the sample types, although CEA was more variable between the sample types for certain patients. The variability was not due to the time delay between EUS-FNA and OR collection or differences in total protein concentrations but may be caused by contamination of the cyst fluid with blood proteins. The classification of each patient based on thresholds for each marker was perfectly consistent between sample types for CA 19-9 and MUC5AC-WGA and mostly consistent for CEA. Therefore, results obtained using OR-collected pancreatic cyst fluid samples should reliably transfer to the clinical setting using EUS-FNA samples.

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Figures

Figure 1

Figure 1

Correlation between OR samples and EUS-FNA samples in the values obtained for three markers. A) For each patient, the value of the indicated marker obtained from the OR sample (y-axis) is plotted with respect to the value obtained from the EUS-FNA sample (x-axis). The best fit linear trendline is indicated. The dashed lines represent the upper limit of the assay linear range for CA 19-9 and MUC5AC-WGA and the clinical threshold of 200 ng/ml for CEA. B) The reproducibility of each assay is indicated by plotting values from one set of data with respect to values from a replicate set. Two representative replicates out of three are shown. Trendlines are presented separately for the OR samples and the EUS-FNA samples, showing similar reproducibilities. The replicate CEA measurements were taken on the same day, and the replicate measurements for the other markers were on different days with different batches of microarrays. RFU, relative fluorescence units.

Figure 2

Figure 2

Variation in total protein concentration and effect on individual measurements. A) Correlation in total protein concentrations between the OR samples and the matched EUS-FNA samples. Each point represents data from one patient, with the y-axis value indicating the OR sample measurement and the x-axis value indicating the EUS-FNA sample measurement. The left panel shows the entire data set, and the right panel shows a detailed view of the low concentration samples. B) Correlations between all markers and total protein concentration. The measurements from the three markers in the EUS-FNA and OR samples (indicated by the row labels) for all patients (indicated by the column labels) were clustered. The value of each measurement is indicated by the color bar. The adjacent rows for each marker show the overall correlation between the EUS-FNA and the OR samples. The total protein concentration has a distinct pattern from any of the markers.

Figure 3

Figure 3

The effect of time lag in sample collection on variation in marker levels and total protein concentrations. For each marker and total protein concentration, the relative difference between the EUS-FNA measurements and the OR measurements are plotted with respect to time differential in sample collection (determined as the number of days between the dates of EUS-FNA sample collection and OR sample collection). The best linear fit is included in each graph.

Figure 4

Figure 4

Classification of the samples based on the marker levels. Thresholds were applied to each of the markers to classify samples as elevated or not elevated in each marker. Using CA 19-9 and MUC5AC-WGA, the patient classification was identical between the EUS-FNA samples and the OR samples. The patient classification using CEA at a threshold of 200 ng/ml showed that only patients 3 and 11 changed classification from the EUS-FNA sample to the OR sample.

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