J Cancer 2017; 8(10):1908-1916. doi:10.7150/jca.17900

Research Paper

Discovery of Non-invasive Glycan Biomarkers for Detection and Surveillance of Gastric Cancer

Ruihuan Qin#1, Junjie Zhao#2, Wenjun Qin1, Zejian Zhang1, Ran Zhao3, Jing Han1, Yupeng yang2, Lixiao Li4, Xuefei Wang✉2, Shifang Ren✉1, Yihong Sun2, Jianxin Gu1

1. Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
3. Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
4. Shimadzu (China) Co., LTD. Shanghai Branch, Shanghai 200052, China
# These authors contributed equally to this work.

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Qin R, Zhao J, Qin W, Zhang Z, Zhao R, Han J, yang Y, Li L, Wang X, Ren S, Sun Y, Gu J. Discovery of Non-invasive Glycan Biomarkers for Detection and Surveillance of Gastric Cancer. J Cancer 2017; 8(10):1908-1916. doi:10.7150/jca.17900. Available from http://www.jcancer.org/v08p1908.htm

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Purpose: Gastric cancer (GC), one of the world's top five most common cancers, is the third leading cause of cancer related death. It is urgent to identify non-invasive biomarkers for GC. The objective of our study was to find out non-invasive biomarkers for early detection and surveillance of GC based on glycomic analysis.

Method: Ethyl esterification derivatization combined with MALDI-TOF MS analysis was employed for the comprehensive serum glycomic analysis in order to investigate glycan markers that would indicate the onset and progression of gastric cancer. Upon the discovery of the candidate biomarkers, those with great potential were further validated in an independent test set. Peaks were acquired by the software of MALDI-MS sample acquisition and processing and analyzed by the software of Progenesis MALDI. 

Results: The differences in glycosylation were found between non-cancer controls and gastric cancer samples: hybrid and multi-branched type (tri-, tetra-antennnary glycans) N-glycans were increased in GC, yet monoantennary, galactose, bisecting type and core fucose N-glycans were decreased. In training set, core fucose (AUC=0.923, 95%CI: 0.8485 to 0.9967) played an excellent diagnostic performance for the early detection of gastric cancer. The diagnostic potential of core fucose was further validated in an independent cohort (AUC=0.854, 95%CI: 0.7592 to 0.9483). Besides, several individual glycan structures reached both statistical criteria (p-values less than 0.05 and AUC scores that were at least moderately accurate) when comparing different stages of GC samples.

Conclusion: We comprehensively evaluate the serum glycan changes in different stages of GC patients including peritoneal metastasis for the first time. We determined several N-glycan biomarkers, some of these have potential in distinguishing the early stage GC from healthy controls, and the others can help to monitor the progression of GC. The findings also enhance understanding of gastric cancer.

Keywords: gastric cancer, glycomic analysis, biomarker, MALDI-TOF-MS, peritoneal metastasis gastric cancer.