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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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Risk of gastric adenocarcinoma and metastasis with protein alterations.H: Healthy controls, NM: patients with no metastasis, M: patients with distant metastasis. Three comparisons were made separately: H vs NM (A, B), H vs M (C, D), and NM vs M (E, F). Subjects were divided into five quintiles based on individual protein levels. The 1st quintile was used as reference and odds ratios of having disease was calculated for upper four quintiles (A, C, E). The chi-squared test for trend in proportions was used to calculate the p-value of overall trend. For a combination of proteins (B, D, F) the combined risk score of each subject was calculated by simply adding risk score from multiple proteins and odds ratios were computed.
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pone.0123985.g002: Risk of gastric adenocarcinoma and metastasis with protein alterations.H: Healthy controls, NM: patients with no metastasis, M: patients with distant metastasis. Three comparisons were made separately: H vs NM (A, B), H vs M (C, D), and NM vs M (E, F). Subjects were divided into five quintiles based on individual protein levels. The 1st quintile was used as reference and odds ratios of having disease was calculated for upper four quintiles (A, C, E). The chi-squared test for trend in proportions was used to calculate the p-value of overall trend. For a combination of proteins (B, D, F) the combined risk score of each subject was calculated by simply adding risk score from multiple proteins and odds ratios were computed.

Mentions: To assess the relationship between GA and different levels of serum proteins, we calculated the odds ratios associated with different levels of serum proteins. Firstly, we divided GA patients without distant metastasis into five quintiles and determined the quintile cutoff values, which were then used to assign the controls into the corresponding quintiles. The bottom quintile was used as reference and compared to each of the other four quintiles. The odds ratios for each protein are charted in Fig 2A. The strongest association is observed with OPN (p-trend<10-20). The odds ratio for GA increases with increasing OPN levels, reaching an OR of ~30 for the 5th quintile. SAA is associated with GA without distant metastasis only in the 5th quintile (OR = 4, p-trend = 0.034). Interestingly, increasing levels of sVCAM1, AGP and GRO levels are associated with reduced risk for GA without metastasis.


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)

Risk of gastric adenocarcinoma and metastasis with protein alterations.H: Healthy controls, NM: patients with no metastasis, M: patients with distant metastasis. Three comparisons were made separately: H vs NM (A, B), H vs M (C, D), and NM vs M (E, F). Subjects were divided into five quintiles based on individual protein levels. The 1st quintile was used as reference and odds ratios of having disease was calculated for upper four quintiles (A, C, E). The chi-squared test for trend in proportions was used to calculate the p-value of overall trend. For a combination of proteins (B, D, F) the combined risk score of each subject was calculated by simply adding risk score from multiple proteins and odds ratios were computed.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123985.g002: Risk of gastric adenocarcinoma and metastasis with protein alterations.H: Healthy controls, NM: patients with no metastasis, M: patients with distant metastasis. Three comparisons were made separately: H vs NM (A, B), H vs M (C, D), and NM vs M (E, F). Subjects were divided into five quintiles based on individual protein levels. The 1st quintile was used as reference and odds ratios of having disease was calculated for upper four quintiles (A, C, E). The chi-squared test for trend in proportions was used to calculate the p-value of overall trend. For a combination of proteins (B, D, F) the combined risk score of each subject was calculated by simply adding risk score from multiple proteins and odds ratios were computed.
Mentions: To assess the relationship between GA and different levels of serum proteins, we calculated the odds ratios associated with different levels of serum proteins. Firstly, we divided GA patients without distant metastasis into five quintiles and determined the quintile cutoff values, which were then used to assign the controls into the corresponding quintiles. The bottom quintile was used as reference and compared to each of the other four quintiles. The odds ratios for each protein are charted in Fig 2A. The strongest association is observed with OPN (p-trend<10-20). The odds ratio for GA increases with increasing OPN levels, reaching an OR of ~30 for the 5th quintile. SAA is associated with GA without distant metastasis only in the 5th quintile (OR = 4, p-trend = 0.034). Interestingly, increasing levels of sVCAM1, AGP and GRO levels are associated with reduced risk for GA without metastasis.

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