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| Metabolomic Study on Serum of Colorectal Adenoma Patients Based on Ultra-high Performance Liquid Chromatography－ Q Exactive Orbitrap Mass Spectrometry |
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| DOI： |
| KeyWord:colorectal adenoma ?ultra-high performance liquid chromatography－Q exactive orbitrap mass spectrometry ?metabolomics ?serum ?biomarkers |
| Author | Institution |
| YANG Bao，LIANG Yun-xiao，HUANG Zong-sheng，TU Xing，ZHOU Chang-yuan，HU Ze-hua，WEN De-jian，ZHANG Qi-song |
1. Medical School，Hubei Minzu University，Enshi ，China;
2. Medical College of Guangxi University，Nanning ，China;
3. Department of Gastroenterology，the People′s Hospital of Guangxi Zhuang Autonomous Region，Nanning ，China;
4. College of Chemistry and Environmental Engineering，Hubei Minzu University，Enshi ，China;
5. Chinese Medicinal Materials Products Quality Supevision and Inspection Center in Wuling Mountainous Area，Hubei Minzu University，Enshi ，China |
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| Abstract: |
| The aim of this paper is to explore the metabolic biomarkers and regulation pathways of colorectal adenoma for better understanding of its pathogenesis．The serum samples of 46 colorectal adenoma patients（age 57.8 ± 10.7） and 45 healthy controls（age 54.4 ± 8.2） were analyzed by ultra-high performance liquid chromatography－Q exactive orbitrap mass spectrometry in an untargeted metabolomic approach. The metabolomics data acquired were analyzed using an unsupervised principal component analysis to visualize the grouping trends and detect outliers．A supervised orthogonal partial least squares discriminant analysis（OPLS－DA） was subsequently utilized to maximize the discrimination．The established OPLS－DA model was validated by permutation test for 200 times．Values of variable importance for projection（VIP） were obtained from the OPLS－DA model．Volcano plots of all metabolites were constructed based on the log2-transformed fold-change and log10-transformed?p-value．Then，the most altered serum metabolites responsible for the discrimination between two groups were screened based on the values of variable importance for projection（VIP?> 1.50） and volcano plot analysis（p?< 0.05 with fold change > 1.50 or fold change < 0.67），and further identified using the mzCloud and HMDB databases．The changed metabolic pathways were analyzed using MetaboAnalyst．ROC curves were used to verify the diagnostic ability of those metabolic biomarkers．The results showed that there were significant differences between the serum metabolic profiles of two groups．20 metabolic biomarkers were screened and identified，including essential amino acids，unsaturated fatty acids，sphingolipids，phospholipids and bile acids，and the corresponding disturbed metabolic pathways were valine，leucine and isoleucine biosynthesis，arachidonic acid metabolism，α-linolenic acid metabolism，linoleic acid metabolism，aminoacyl-tRNA biosynthesis，sphingolipid metabolism，glycerophospholipid metabolism and tryptophan metabolism．Among the 20 metabolic biomarkers，juniperic acid，arachidonic acid，creatinine，valine，leucine，tryptophan，linolenic acid，taurochodeoxycholic acid and LysoPC（20∶3） showed high specificity and sensitivity with their areas under the ROC curves（AUC）greater than 0.90，which meant strong diagnostic ability and potential clinical application in serum-based metabolomics screening for colorectal adenoma．This study provides some basic data that could be used to clarify the metabolic characteristics of colorectal adenoma． |
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