| Colorectal cancer(CRC) which including colon cancer and rectumcancer, is a common gastrointestinal cancer with the combined effects ofmultiple factors. In recent years, the incidence and mortality of colorectalcancer is rising in our country. It has the complex process with multi-geneand long-term, its pathogenesis is still not fully understood, and there aremany limitations in the traditional checks. Numberous studies havedemonstrated that the metabolite profiles of various tumors are highlycorrelated with tumor type, proliferation, metabolic activity and cell death.Therefore, metabolomics used in exploring the early diagnosis markers ofcolorectal cancer become a hot topic in recent years. It has been confirmedthat the levels of a variety of metabolites including tryptophan in patientswith colorectal cancer have changed. However, there is still no in-depthstudy of its complete metabolic pathway.The blood and urine samples were collected from the309Hospital ofPeople’s Liberation Army in October2012~July2013, including40CRCpatients who was diagnosed by pathology and20healthy controls.Collect and analyze data by using liquid chromatography-tandem massspectrometry (LC-MS/MS) technology and V.1.5.1analysis systems. Theaim is to determinate the level of tryptophan metabolites in urine and serumfrom colorectal cancer patients with different stages and healthy controls,and also to evaluate the metabolic activity of the process by thekynurenine/tryptophan ratio. As a result, the tryptophan and its metaboliteslevel were not significantly correlated with age and gender. Tryptophan metabolic profiling of urine: The levels ofKYN(Kynurenine), HK(3-hydroxykynurenine), HAA(3-hydroxyanthranilicacid), ILA(indole-3-lactic acid), IPA(indole-3-propionic acid) andAA(Anthranilic acid) in colorectal cancer patients urine were significantlyincreased (P<0.05, P<0.001); whereas the levels of Trp(Tryptophan) andKA(kynurenic acid) of patients with colorectal cancer decreasedsignificantly compared with control group (P<0.05); kynurenine/tryptophanratio in colorectal cancer patients had significantly increased (P<0.001), thelevel of HAA in CRC patients with advanced stage was significantly highercompared with the early stage (P<0.05).Tryptophan metabolic profiling of serum: The levels of Serotomin,AA(Anthranilic acid), HAA(3-hydroxyanthranilic acid),IAA(Indole-3-acetic acid), HIAA (5-Hydroxy-indole-3-acetic acid) weresignificantly increased in the CRC patients(P<0.05); the levels ofTrp(Tryptophan) and XA(Xanthurenic acid) were decreased in the serum ofCRC patients compared with healthy controls(P<0.05). The serum level ofAA in the advanced stage CRC patients was significantly increased(P<0.05).The metabolic pathway of tryptophan in the occurrence andprogression of CRC occurs dynamic disturbance. The levels of HAA inurine and the levels of AA in serum can significantly distinguish healthycontrols from CRC patients and CRC patients of early stage and advancedstage. Because the ELISA kits are not yet fully mature, we detected thelevel of AA in serum. Re-collected the serum from20colorectal cancerpatients and15normal controls. The result showed that the level of AA inserum are significantly higher than the control groups, these molecules maybe the screening markers for colorectal cancer. Quantitative tryptophanmetabolites by using LC-MS/MS can lay the foundation for the research ofhyperuricemia pathogenesis, prediction and prevention, and it is expectedto be the assisted method to diagnosis CRC. |
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