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ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

Lin C, Wu WC, Zhao GC, Wang DS, Lou WH, Jin DY - Medicine (Baltimore) (2016)

Bottom Line: Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer.Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria.It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China.

ABSTRACT
Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

No MeSH data available.


Related in: MedlinePlus

APOA-I levels were significant difference between CA19-9 negative PDAC patients, CA19-9 positive PDAC patients, and normal individuals.∗: P < 0.05; ∗∗∗:P < 0.001. APOA-I = apolipoprotein A-I, PDAC = pancreatic ductal adenocarcinoma.
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Figure 1: APOA-I levels were significant difference between CA19-9 negative PDAC patients, CA19-9 positive PDAC patients, and normal individuals.∗: P < 0.05; ∗∗∗:P < 0.001. APOA-I = apolipoprotein A-I, PDAC = pancreatic ductal adenocarcinoma.

Mentions: Among the identified proteins, APOA-I and TF were found to be associated to pancreatic cancer. However, whether they could be the biomarkers for CA19-9 negative PDAC has not been reported. For this reason, we directly assessed its level of expression by ELISA to validate our proteomic results. We used the entire 78 samples collected. A statistical significant difference between the CA19-9 positive PDAC group, CA19-9 negative PDAC group, and normal control group was seen in serum concentrations of APOA-I (435.1 ± 49.5 ng/mL in the CA19-9 positive PDAC group, 529.6 ± 84.0 ng/mL in the CA19-9 negative PDAC group, and 555.0 ± 87.1 ng/mL in the normal control group, (P < 0.001) and TF(3870.8 ± 1033.3 ng/mL in the CA19-9 positive PDAC group, 2920.8 ± 1097.6 ng/mL in the CA19-9 negative PDAC group, and 2769.5 ± 1329.9ng/mL in normal control, P = 0.002) (Figs. 1 and 2). The difference in APOA-I level between CA19-9 positive PDAC group and CA19-9 negative PDAC group also reached statistical significance (P < 0.001), suggesting the specificity of this marker for CA19-9 negative PDAC. The cutoff value and corresponding sensitivity and specificity values for both biomarkers were shown in Table 1


ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

Lin C, Wu WC, Zhao GC, Wang DS, Lou WH, Jin DY - Medicine (Baltimore) (2016)

APOA-I levels were significant difference between CA19-9 negative PDAC patients, CA19-9 positive PDAC patients, and normal individuals.∗: P < 0.05; ∗∗∗:P < 0.001. APOA-I = apolipoprotein A-I, PDAC = pancreatic ductal adenocarcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979862&req=5

Figure 1: APOA-I levels were significant difference between CA19-9 negative PDAC patients, CA19-9 positive PDAC patients, and normal individuals.∗: P < 0.05; ∗∗∗:P < 0.001. APOA-I = apolipoprotein A-I, PDAC = pancreatic ductal adenocarcinoma.
Mentions: Among the identified proteins, APOA-I and TF were found to be associated to pancreatic cancer. However, whether they could be the biomarkers for CA19-9 negative PDAC has not been reported. For this reason, we directly assessed its level of expression by ELISA to validate our proteomic results. We used the entire 78 samples collected. A statistical significant difference between the CA19-9 positive PDAC group, CA19-9 negative PDAC group, and normal control group was seen in serum concentrations of APOA-I (435.1 ± 49.5 ng/mL in the CA19-9 positive PDAC group, 529.6 ± 84.0 ng/mL in the CA19-9 negative PDAC group, and 555.0 ± 87.1 ng/mL in the normal control group, (P < 0.001) and TF(3870.8 ± 1033.3 ng/mL in the CA19-9 positive PDAC group, 2920.8 ± 1097.6 ng/mL in the CA19-9 negative PDAC group, and 2769.5 ± 1329.9ng/mL in normal control, P = 0.002) (Figs. 1 and 2). The difference in APOA-I level between CA19-9 positive PDAC group and CA19-9 negative PDAC group also reached statistical significance (P < 0.001), suggesting the specificity of this marker for CA19-9 negative PDAC. The cutoff value and corresponding sensitivity and specificity values for both biomarkers were shown in Table 1

Bottom Line: Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer.Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria.It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China.

ABSTRACT
Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

No MeSH data available.


Related in: MedlinePlus