[Animal Modeling] - Metabolomics Analysis of Tree Shrew Breast Tumor Model

  Objective: To study the changes in metabolomics during the occurrence and development of breast tumors in tree shrews, explore the close relationship between changes in metabolic substances in the body and tumor occurrence and development, and screen for biomarkers reflecting the progression of breast tumors.

  Method: 20 tree shrews were orally administered with 0.15 mg/kg of 7,12-dimethylbenzoanthracene (DMBA) for 3 consecutive times with a 15 day interval, and a high-fat and high sugar diet was added. The induction experiment was observed for 24 months or until the tree shrews developed breast tumors. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) was used to perform non targeted determination of serum metabolites in tree shrews induced by DMBA with breast tumors, tree shrews without breast tumors induced by DMBA, and 12 normal tree shrews without induction. Principal component analysis (PCA) was performed Orthogonal partial least squares analysis (OPLS-DA) and other multidimensional statistical analyses were used to further compare the differences between groups using t-tests. Differential metabolites were screened using VIP>1 and P<0.05 standards, and significant changes were identified using the HMDB online database. Finally, the Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied The pathway database enriches metabolic related gene regulatory pathways.

  The incidence of breast tumors in tree shrews induced by DMBA was 40% (8/20). Compared with the normal control group, 30 metabolic differential products were detected in the serum of tree shrews in the DMBA modeling tumor group, of which 18 were down regulated and 12 were up regulated, and the differences were statistically significant (VIP>1, P<0.05); 7="" 11="" 18="" kegg="" pathway="" analysis="" revealed="" significant="" changes="" in="" four="" metabolic="" pathways:="" glutamate="" glyceride="" citric="" acid="" and="" alanine="" metabolism.="" compared="" with="" the="" non="" tumor="" group="" formed="" by="" dmba="" differential="" products="" were="" detected="" modeling="" of="" which="" down="" regulated="" up="" statistically="" differences="" vip="">1, P<0.05); 14="" 17="" 31="" kegg="" pathway="" analysis="" revealed="" significant="" changes="" in="" the="" citrate="" cycle="" and="" glutamate="" metabolism="" pathways.="" compared="" with="" normal="" control="" dmba="" modeling="" group="" without="" tumor="" formation="" detected="" metabolic="" differential="" of="" which="" were="" down="" regulated="" up="" statistically="" differences="" vip="">1, P<0.05); KEGG pathway analysis found that the citric acid cycle, glutamate metabolism, and glyceride metabolism