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Inflammatory serum proteins are severely altered in metastatic gastric adenocarcinoma patients from the Chinese population.

Wang J, Ma R, Sharma A, He M, Xue J, Wu J, Dun B, Li G, Wang X, Ji M, She JX, Tang J - PLoS ONE (2015)

Bottom Line: The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA.Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls.These results suggest that several serum proteins are directly related to the severity of gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, Jiangsu Province, China.

ABSTRACT

Background: Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.

Methods: Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.

Results: The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.

Conclusions: These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.

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ROC Curves to evaluate the utility of six candidate biomarkers for GA and associated distant metastasis.H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. Four comparisons were made separately: H vs GA (A), H vs NM (B), H vs M (C) and NM vs M (D). For comparisons with non-metastasis and healthy controls, the best AUC values are 0.833 (sVACM1) and 0.786 (OPN). For comparisons with metastasis and healthy controls, the best AUC values are 0.931 (OPN) and 0.834 (SAA).
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pone.0123985.g003: ROC Curves to evaluate the utility of six candidate biomarkers for GA and associated distant metastasis.H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. Four comparisons were made separately: H vs GA (A), H vs NM (B), H vs M (C) and NM vs M (D). For comparisons with non-metastasis and healthy controls, the best AUC values are 0.833 (sVACM1) and 0.786 (OPN). For comparisons with metastasis and healthy controls, the best AUC values are 0.931 (OPN) and 0.834 (SAA).

Mentions: The potential utility of serum proteins as GA biomarkers was evaluated using the areas-under-curve (AUC) in receiver-operating-characteristic (ROC) curves. We first evaluated each of the six proteins for their ability to distinguish: 1) all GA patients from controls (H vs GA), 2) non-metastatic patients from healthy controls (H vs NM), 3) metastatic patients from healthy controls (H vs M), and 4) metastatic from non-metastatic patients (NM vs M). As shown in Fig 3, individual proteins generally do not possess great diagnostic value with a few exceptions. The best AUC values are 0.835 (OPN) in the H vs GA comparison, 0.833 (sVCAM1) and 0.823 (AGP) in the H vs NM comparison, 0.931 (OPN) and 0.834 (SAA) in the H vs M comparison, and 0.788 (AGP) and 0.771 (CRP) in the NM vs M comparison.


Inflammatory serum proteins are severely altered in metastatic gastric adenocarcinoma patients from the Chinese population.

Wang J, Ma R, Sharma A, He M, Xue J, Wu J, Dun B, Li G, Wang X, Ji M, She JX, Tang J - PLoS ONE (2015)

ROC Curves to evaluate the utility of six candidate biomarkers for GA and associated distant metastasis.H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. Four comparisons were made separately: H vs GA (A), H vs NM (B), H vs M (C) and NM vs M (D). For comparisons with non-metastasis and healthy controls, the best AUC values are 0.833 (sVACM1) and 0.786 (OPN). For comparisons with metastasis and healthy controls, the best AUC values are 0.931 (OPN) and 0.834 (SAA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401731&req=5

pone.0123985.g003: ROC Curves to evaluate the utility of six candidate biomarkers for GA and associated distant metastasis.H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. Four comparisons were made separately: H vs GA (A), H vs NM (B), H vs M (C) and NM vs M (D). For comparisons with non-metastasis and healthy controls, the best AUC values are 0.833 (sVACM1) and 0.786 (OPN). For comparisons with metastasis and healthy controls, the best AUC values are 0.931 (OPN) and 0.834 (SAA).
Mentions: The potential utility of serum proteins as GA biomarkers was evaluated using the areas-under-curve (AUC) in receiver-operating-characteristic (ROC) curves. We first evaluated each of the six proteins for their ability to distinguish: 1) all GA patients from controls (H vs GA), 2) non-metastatic patients from healthy controls (H vs NM), 3) metastatic patients from healthy controls (H vs M), and 4) metastatic from non-metastatic patients (NM vs M). As shown in Fig 3, individual proteins generally do not possess great diagnostic value with a few exceptions. The best AUC values are 0.835 (OPN) in the H vs GA comparison, 0.833 (sVCAM1) and 0.823 (AGP) in the H vs NM comparison, 0.931 (OPN) and 0.834 (SAA) in the H vs M comparison, and 0.788 (AGP) and 0.771 (CRP) in the NM vs M comparison.

Bottom Line: The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA.Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls.These results suggest that several serum proteins are directly related to the severity of gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, Jiangsu Province, China.

ABSTRACT

Background: Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.

Methods: Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.

Results: The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.

Conclusions: These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.

Show MeSH
Related in: MedlinePlus