Metabolomic Detection Between Pancreatic Cancer and Liver Metastasis Nude Mouse Models Constructed by Using the PANC1-KAI1/CD₈₂ Cell Line

Abstract

Background: Pancreatic cancer (PC) has a poor prognosis and is prone to liver metastasis. The KAI1/CD82 gene inhibits PC metastasis. This study aimed to explore differential metabolites and enrich the pathways in serum samples between PC and liver metastasis nude mouse models stably expressing KAI1/CD82. Methods: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed for the first time. This cell line was used to construct 3 PC nude mouse models and 3 liver metastasis nude mouse models. The different metabolites and Kyoto encyclopedia of genes and genomes (KEGG) and human metabolome database (HMDB) enrichment pathways were analyzed using the serum samples of the 2 groups of nude mouse models on the basis of untargeted ultra-performance liquid chromatography-tandem mass spectrometry platform. Results: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed successfully, and all nude mouse models survived and developed cancers. Among the 1233 metabolites detected, 18 metabolites (9 upregulated and 9 downregulated) showed differences. In agreement with the literature data, the most significant differences between both groups were found in the levels of bile acids (taurocholic acid, chenodeoxycholic acid), glycine, prostaglandin E2, vitamin D, guanosine monophosphate, and inosine. Bile recreation, primary bile acid biosynthesis, and purine metabolism KEGG pathways and a series of HMDB pathways ( P < .05) contained differential metabolites that may be associated with liver metastasis from PC. However, the importance of these metabolites on PC liver metastases remains to be elucidated. Conclusions: Our findings suggested that the metabolomic approach may be a useful method to detect potential biomarkers in PC.

Bifidobacterium animalis subsp. lactis F1–7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR

“…Then the identified metabolites were classified pathways based on the KEGG pathway database. The pathway through which metabolites were significantly regulated was introduced into MSEA, and their significance was determined by hypergeometric test’s p -values …”

“…The pathway through which metabolites were significantly regulated was introduced into MSEA, and their significance was determined by hypergeometric test's p-values. 21 Microbiota DNA Extraction and 16S rRNA Sequencing Analysis. The total microbial genomic DNA was extracted from 50 mg of feces samples of mice using the E.Z.N.A.…”

Bile Acids and Microbiota Interplay in Pancreatic Cancer

“…The most notable differences were observed in BA levels, particularly TCA and CDCA, prostaglandin E2, glycine, guanosine monophosphate, vitamin D, and inosine. These findings along with the relevant enriched pathways in the Kyoto Encyclopaedia of Genes and Genome (KEGG) as well as a set of human metabolome database (HMDB) are predicted to assist early detection and improve prognosis in PC patients with liver metastasis [106].…”