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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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Boxplots representing the serum protein levels in patient subgroups and healthy controls.Subgroups are defined based on the presence of cancer (A), metastasis status (B), and cancer stage (C). H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. The pairwise correlations between all six proteins are shown in H, NM, and M subgroups (D). Correlations between individual protein levels were computed using Pearson correlation coefficient. Clustering and visualization of correlation matrix was performed using hierarchical clustering method and heatmap. Overall strong positive correlations were observed in both the GA patients with distant metastasis and without distant metastasis as compared to healthy controls.
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pone.0123985.g001: Boxplots representing the serum protein levels in patient subgroups and healthy controls.Subgroups are defined based on the presence of cancer (A), metastasis status (B), and cancer stage (C). H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. The pairwise correlations between all six proteins are shown in H, NM, and M subgroups (D). Correlations between individual protein levels were computed using Pearson correlation coefficient. Clustering and visualization of correlation matrix was performed using hierarchical clustering method and heatmap. Overall strong positive correlations were observed in both the GA patients with distant metastasis and without distant metastasis as compared to healthy controls.

Mentions: Six candidate proteins (OPN, sVCAM1, SAA, CRP, AGP and GRO) were measured in serum samples from 219 newly-diagnosed patients with gastric adenocarcinoma and 333 healthy control subjects using Luminex multiplex assays. The raw data are presented as box plots in Fig 1A. Three proteins (OPN, SAA and CRP) were significantly increased in GA patients compared to healthy controls. The mean OPN level is 2.4-fold higher in GA patients than controls (p<10-42). The mean SAA level is 3.7-fold higher in GA patients than controls (p<10-14), while the increase in mean CRP level is barely significant (FC = 1.3, p = 0.029). sVCAM1 is lower in GA patients than controls (FC = 0.69, p<10-32). Furthermore, the mean level of AGP is also lower in GA patients (FC = 0.67, p<10-13). No significant difference was revealed for GRO between GA patients and controls.


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)

Boxplots representing the serum protein levels in patient subgroups and healthy controls.Subgroups are defined based on the presence of cancer (A), metastasis status (B), and cancer stage (C). H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. The pairwise correlations between all six proteins are shown in H, NM, and M subgroups (D). Correlations between individual protein levels were computed using Pearson correlation coefficient. Clustering and visualization of correlation matrix was performed using hierarchical clustering method and heatmap. Overall strong positive correlations were observed in both the GA patients with distant metastasis and without distant metastasis as compared to healthy controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123985.g001: Boxplots representing the serum protein levels in patient subgroups and healthy controls.Subgroups are defined based on the presence of cancer (A), metastasis status (B), and cancer stage (C). H: Healthy controls, GA: Gastric Adenocarcinoma, NM: patients with no metastasis, M: patients with distant metastasis. The pairwise correlations between all six proteins are shown in H, NM, and M subgroups (D). Correlations between individual protein levels were computed using Pearson correlation coefficient. Clustering and visualization of correlation matrix was performed using hierarchical clustering method and heatmap. Overall strong positive correlations were observed in both the GA patients with distant metastasis and without distant metastasis as compared to healthy controls.
Mentions: Six candidate proteins (OPN, sVCAM1, SAA, CRP, AGP and GRO) were measured in serum samples from 219 newly-diagnosed patients with gastric adenocarcinoma and 333 healthy control subjects using Luminex multiplex assays. The raw data are presented as box plots in Fig 1A. Three proteins (OPN, SAA and CRP) were significantly increased in GA patients compared to healthy controls. The mean OPN level is 2.4-fold higher in GA patients than controls (p<10-42). The mean SAA level is 3.7-fold higher in GA patients than controls (p<10-14), while the increase in mean CRP level is barely significant (FC = 1.3, p = 0.029). sVCAM1 is lower in GA patients than controls (FC = 0.69, p<10-32). Furthermore, the mean level of AGP is also lower in GA patients (FC = 0.67, p<10-13). No significant difference was revealed for GRO between GA patients and controls.

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