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¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

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OPLS-DA scores and coefficient-colored loadings plots (A, B) for 3 weeks-old C57 mice (■) and Rip1-Tag2 (●). (R2X=88.5%, Q2Y=78.3%)
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Figure 3: OPLS-DA scores and coefficient-colored loadings plots (A, B) for 3 weeks-old C57 mice (■) and Rip1-Tag2 (●). (R2X=88.5%, Q2Y=78.3%)

Mentions: We compared the sera metabolic profiles in morphologically normal Rip1-Tag2 mice (3 weeks old) and background mice of C57, in order to discover the metabolic difference induced by SV 40 gene transplantation. PCA was firstly done according to the 1H NMR integral data at δ 0.5-4.5 in order to highlight the contribution of metabolites with low molecular weight (in Supplementary Material: Fig. S2), in which obvious separation between these two types of mice was observed, demonstrating the distinct metabolic phenotype associated with SV 40 gene transplantation in Rip1-Tag2 mice. Clear grouping between Rip1-Tag2 and C57 through t1 dimension was also found in OPLS-DA model (Fig. 3A, R2X=88.5%, Q2Y=78.3%). We can observe that lactate, LDL+VLDL and choline increased, and acetate, glucose, taurine, glycine and myo-inositol decreased in Rip1-Tag2 transgenic mice (Fig. 3B). All the selected metabolites showed statistical significance between Rip1-Tag2 and C57 mice, which may serve as biomarkers associated with SV 40 gene transplantation in Rip1-Tag2 mice (Table 1).


¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

OPLS-DA scores and coefficient-colored loadings plots (A, B) for 3 weeks-old C57 mice (■) and Rip1-Tag2 (●). (R2X=88.5%, Q2Y=78.3%)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400390&req=5

Figure 3: OPLS-DA scores and coefficient-colored loadings plots (A, B) for 3 weeks-old C57 mice (■) and Rip1-Tag2 (●). (R2X=88.5%, Q2Y=78.3%)
Mentions: We compared the sera metabolic profiles in morphologically normal Rip1-Tag2 mice (3 weeks old) and background mice of C57, in order to discover the metabolic difference induced by SV 40 gene transplantation. PCA was firstly done according to the 1H NMR integral data at δ 0.5-4.5 in order to highlight the contribution of metabolites with low molecular weight (in Supplementary Material: Fig. S2), in which obvious separation between these two types of mice was observed, demonstrating the distinct metabolic phenotype associated with SV 40 gene transplantation in Rip1-Tag2 mice. Clear grouping between Rip1-Tag2 and C57 through t1 dimension was also found in OPLS-DA model (Fig. 3A, R2X=88.5%, Q2Y=78.3%). We can observe that lactate, LDL+VLDL and choline increased, and acetate, glucose, taurine, glycine and myo-inositol decreased in Rip1-Tag2 transgenic mice (Fig. 3B). All the selected metabolites showed statistical significance between Rip1-Tag2 and C57 mice, which may serve as biomarkers associated with SV 40 gene transplantation in Rip1-Tag2 mice (Table 1).

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

Show MeSH
Related in: MedlinePlus