J Cancer 2020; 11(16):4641-4651. doi:10.7150/jca.41250

Research Paper

Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples

Xiaohan Zhang1, Xiuyun Shi1, Xin Lu1, Yiqun Li1, Chao Zhan2, Muhammad Luqman Akhtar1, Lijun Yang1, Yunfan Bai1, Jianxiang Zhao1, Yu Wang1, Yuanfei Yao2, Yu Li1✉, Huan Nie1✉

1. School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
2. The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China.

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Zhang X, Shi X, Lu X, Li Y, Zhan C, Akhtar ML, Yang L, Bai Y, Zhao J, Wang Y, Yao Y, Li Y, Nie H. Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples. J Cancer 2020; 11(16):4641-4651. doi:10.7150/jca.41250. Available from http://www.jcancer.org/v11p4641.htm

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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The metabolomic approaches are developed to discover the novel biomarkers of PDAC.

Methods: 550 preoperative, postoperative PDAC and normal controls (NCs) serums were employed to characterize metabolic alterations in training and validation sets by LC-MS.

Results: The results of PLS-DA analysis indicated that three groups could be distinguished clearly and the post-PDAC group is adjacent to a normal group as compared with pre-PDAC group. Further results showed that histidinyl-lysine significantly increased whereas docosahexaenoic acid and LysoPC (14:0) decreased in pre-PDAC patients as compared with NCs. And these three markers had a significant tendency to recover after tumor resection. The validation set results revealed that for CA19-9 negative patients, 92.3% (12/13) of them can be screened using these three metabolites. The combination of these markers could significantly improve the diagnostic performance for PDAC, with higher sensitivity (0.93), specificity (0.92) and AUC (0.97). Moreover, network and pathways analyses explored the latent relationship among differential metabolites. The glycerolipid metabolism and primary bile acid synthesis showed variation in network and pathway analysis.

Conclusions: These three markers combined with CA199 displayed high sensitivity and specificity for detecting PDAC patients from NCs. The results indicated that these three metabolites could be regarded as potential biomarkers to distinguish PDAC from NCs.

Keywords: Metabolomics, Pancreatic Ductal Adenocarcinoma, Multivariate analysis, Biomarkers