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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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A summary of the biochemical pathway changes in the pathological progression of Rip1-Tag2 transgenic mice. Blue represents the changes at 8 weeks, green represents the changes at 10 weeks and orange represents the changes at 14 weeks.
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Figure 6: A summary of the biochemical pathway changes in the pathological progression of Rip1-Tag2 transgenic mice. Blue represents the changes at 8 weeks, green represents the changes at 10 weeks and orange represents the changes at 14 weeks.

Mentions: From the histopathological characteristics shown in Fig. 1, we could find the noticeable progression of tumor development, and the histopathological changes in every stage showed great reproducibility and were consistent with the previous results 22, 24, 25. Fig. 4 demonstrated the metabolic progression trajectory from 3 weeks to 14 weeks, which revealed the serum metabolic changes with the tumor development. However, the samples at 3 weeks and 5 weeks were inseparable due to few metabolic differences between normal and proliferation stages, which may be a result of slight proliferation of pancreatic islet β cells at 5 weeks. Multivariate data analyses were performed to identify the metabonomic biomarkers for characterizing the different stages of tumor development. By comparing with sera metabonomic profiles in different types of tumor 28-33, it was found that the increased methionine, and decreased DMA, taurine, glycine and MI were unique characteristics of the serum metabolic profiles in Rip1-Tag2 mice. A general metabolic pathway was drawn according to the changed metabolites (Fig. 6), in which mechanism of glucose, lipid, choline and amino acid were obviously displayed and the mutual transformations between each other were shown in general.


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)

A summary of the biochemical pathway changes in the pathological progression of Rip1-Tag2 transgenic mice. Blue represents the changes at 8 weeks, green represents the changes at 10 weeks and orange represents the changes at 14 weeks.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: A summary of the biochemical pathway changes in the pathological progression of Rip1-Tag2 transgenic mice. Blue represents the changes at 8 weeks, green represents the changes at 10 weeks and orange represents the changes at 14 weeks.
Mentions: From the histopathological characteristics shown in Fig. 1, we could find the noticeable progression of tumor development, and the histopathological changes in every stage showed great reproducibility and were consistent with the previous results 22, 24, 25. Fig. 4 demonstrated the metabolic progression trajectory from 3 weeks to 14 weeks, which revealed the serum metabolic changes with the tumor development. However, the samples at 3 weeks and 5 weeks were inseparable due to few metabolic differences between normal and proliferation stages, which may be a result of slight proliferation of pancreatic islet β cells at 5 weeks. Multivariate data analyses were performed to identify the metabonomic biomarkers for characterizing the different stages of tumor development. By comparing with sera metabonomic profiles in different types of tumor 28-33, it was found that the increased methionine, and decreased DMA, taurine, glycine and MI were unique characteristics of the serum metabolic profiles in Rip1-Tag2 mice. A general metabolic pathway was drawn according to the changed metabolites (Fig. 6), in which mechanism of glucose, lipid, choline and amino acid were obviously displayed and the mutual transformations between each other were shown in general.

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