New serum biomarker identification and analysis by mass spectrometry in cervical precancerous lesion and acute cervicitis in South China
Received 12 February 2019
Accepted for publication 29 May 2019
Published 4 July 2019 Volume 2019:11 Pages 6151—6162
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr Chien-Feng Li
Feng Qiu,*,1 Bingsen Su,*,2 Zhao Li,3 Wenke Chen,1 Longbing Cao,1 Fu Chen,4 Dongdong Liu,4 Jingling He,5 Ni Lin3
1Department of Laboratory Medicine, Nanhai Hospital, Southern Medical University, Foshan, Guangdong 528244, People’s Republic of China; 2Department of Laboratory Medicine, Zhongshan Torch Development Zone Hospital, Zhongshan, Guangdong 528437, People’s Republic of China; 3Department of General Practice Center, Nanhai Hospital, Southern Medical University, Foshan, Guangdong 528244, People’s Republic of China; 4Department of Laboratory Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, People’s Republic of China; 5Department of Gynecology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, People’s Republic of China
*These authors contributed equally to this work
Background: According to the statistics of WHO/IARC, cervical cancer (CC) has become the fourth malignant cancer of female worldwide and it is one of the main causes of death of women in developing countries.
Purpose: Potential plasma and metabolic biomarkers for CC precancerous lesions and cervicitis were indicated by LC-MS techniques, and their underlying mechanisms and functions were analyzed.
Methods: Plasma samples were selected from healthy people (control), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), CC, and post-treatment patients. All polypeptide types and sequences were detected by LC-MS/MS and the results were normalized by using Pareto-scaling. Potential metabolic biomarkers were screened by applying MetaboAnalyst 4.0 software and XCMS software, and analysis of variance and enrichment analysis were performed. Metabolic pathway analysis and functional enrichment analysis were used to further investigate the significance and pathological mechanisms of potential biomarkers.
Results: Compared with healthy people, 9 differentially expressed metabolites were screened, 4 of which were up-regulated and 5 were down-regulated. LSIL group screened 7 differentially expressed metabolites, 5 of which were up-regulated and 2 were down-regulated; CC group screened 12 differentially expressed metabolites were screened, of which 9 were up-regulated and 3 were down-regulated. Eight differentially expressed metabolites were screened in the IF group, of which 5 showed up-regulation and 3 showed down-regulation. In functional enrichment analysis, differential metabolism was found to be associated with addition and coagulation cascades. Among all potential biomarkers, 2-amino-3-methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg, 2-amino-3 -Methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg can be used as predictors of precancerous lesions at different stages of CC. Among all biomarkers, 6α-fluoro-11β1,17-dihydroxypren-4-ene-3,20-dione has higher expression in the CC and HSIL groups and lower expression in the treatment group.
Conclusion: By applying molecular markers to assess the progression of the disease, the accuracy and specificity of the diagnosis can be improved, which has certain prospects in clinical applications.
Keywords: cervical precancerous lesion, acute cervicitis, LC-MS, metabonomics, serum biomarkers
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