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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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Related in: MedlinePlus

The utility of protein combinations to distinguish GA and associated distant metastasis.For multi-protein models, linear discriminate analysis was performed using 3 protein and 4 protein combinations. The diagnostic performance of each model was evaluated using leave one out cross validation method. The utility of serum proteins as cancer biomarkers was evaluated using the area-under-curve (AUC) of the ROC curves for different models. Several protein combinations possess excellent diagnostic value (AUC >0.9) in distinguishing both non-metastatic and metastatic samples from healthy controls.
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pone.0123985.g004: The utility of protein combinations to distinguish GA and associated distant metastasis.For multi-protein models, linear discriminate analysis was performed using 3 protein and 4 protein combinations. The diagnostic performance of each model was evaluated using leave one out cross validation method. The utility of serum proteins as cancer biomarkers was evaluated using the area-under-curve (AUC) of the ROC curves for different models. Several protein combinations possess excellent diagnostic value (AUC >0.9) in distinguishing both non-metastatic and metastatic samples from healthy controls.

Mentions: Subsequently, we attempted to improve the AUC values using combinations of proteins. Combined risk score was calculated for each subject by adding the quintile odds ratios for multiple proteins as described above. The potential diagnostic value of combined risk score was evaluated using the ROC curves. As shown in Fig 4, multiple combinations can improve the AUC values for all four comparisons. For the H vs NM comparison the three protein model with best AUC of 0.935 is OPN-sVCAM1-AGP and the four protein model with best AUC of 0.946 is OPN-sVCAM1-AGP-SAA. For the H vs M comparison the three protein model with best AUC of 0.962 is OPN-sVCAM1-SAA and the four protein model with best AUC of 0.963 is OPN-sVCAM1- SAA-AGP model. However, the best models for NM vs M comparison only had AUC around 0.833.


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)

The utility of protein combinations to distinguish GA and associated distant metastasis.For multi-protein models, linear discriminate analysis was performed using 3 protein and 4 protein combinations. The diagnostic performance of each model was evaluated using leave one out cross validation method. The utility of serum proteins as cancer biomarkers was evaluated using the area-under-curve (AUC) of the ROC curves for different models. Several protein combinations possess excellent diagnostic value (AUC >0.9) in distinguishing both non-metastatic and metastatic samples from healthy controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123985.g004: The utility of protein combinations to distinguish GA and associated distant metastasis.For multi-protein models, linear discriminate analysis was performed using 3 protein and 4 protein combinations. The diagnostic performance of each model was evaluated using leave one out cross validation method. The utility of serum proteins as cancer biomarkers was evaluated using the area-under-curve (AUC) of the ROC curves for different models. Several protein combinations possess excellent diagnostic value (AUC >0.9) in distinguishing both non-metastatic and metastatic samples from healthy controls.
Mentions: Subsequently, we attempted to improve the AUC values using combinations of proteins. Combined risk score was calculated for each subject by adding the quintile odds ratios for multiple proteins as described above. The potential diagnostic value of combined risk score was evaluated using the ROC curves. As shown in Fig 4, multiple combinations can improve the AUC values for all four comparisons. For the H vs NM comparison the three protein model with best AUC of 0.935 is OPN-sVCAM1-AGP and the four protein model with best AUC of 0.946 is OPN-sVCAM1-AGP-SAA. For the H vs M comparison the three protein model with best AUC of 0.962 is OPN-sVCAM1-SAA and the four protein model with best AUC of 0.963 is OPN-sVCAM1- SAA-AGP model. However, the best models for NM vs M comparison only had AUC around 0.833.

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