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Serum Microbiome Analysis as a Tool Towards Targeted Biomarker for Gastric Cancer

31 Pages Posted: 16 Nov 2018

See all articles by Zhao-Gang Dong

Zhao-Gang Dong

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Bin Chen

Beihang University (BUAA) - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine

Ding Wang

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Hong-wei Pan

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Min Liu

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Yong-mei Yang

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Ming-jin Zou

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jun-jie Yang

Qilu Normal University - College of Life Science

Ke Xiao

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Rui Zhao

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Xin Zheng

Shandong University - Department of Clinical Laboratory; Shandong University - Shandong Province Key Laboratories of Medicine and Health

Lei Zhang

Beihang University (BUAA) - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine

Yi Zhang

Shandong University - Department of Clinical Laboratory; Shandong Provincial Medicine and Health - Key Laboratory of Tumor Marker Translational Medicine; Shandong University - Shandong Province Key Laboratories of Medicine and Health

More...

Abstract

Background: Gastric cancer (GC) has been found to be associated with alterations in the composition of microbiome. However, little is known about the composition of blood microbiome in GC patients. Our aim is to characterize blood microbiome in GC patients and evaluate its potential value as biomarkers.  

Methods: 71 GC, 6 atypical hyperplasia (AH), 11 chronic gastritis (CG), and 13 healthy controls (HC) were analyzed for serum microbiome. Meanwhile, serum CEA, CA19-9, and CA72-4, were also detected by electrochemiluminescence assay. Finally, we characterized serum bacterial with significant difference, identified microbial markers and constructed GC classifier.  

Findings: The structure of serum microbiome in GC was significantly differed from all other groups, and alpha diversity of serum microbial was decreased from HC to GC. Serum microbiome was significantly correlated to TNM stage, lymphatic metastasis, tumor diameter, and invasion depth in GC. Six genus or species were selected as microbial biomarkers for diagnosis analysis, including Acinetobacter, Bacteroides, Sphingomonas, Comamonas, Haemophilus parainfluenzae, and Pseudomonas stutzeri. ROC analysis showed that AUC of six microbial biomarkers combination was 0.867 (95% CI: 0.775-0.931) with a sensitivity 80.3% and specificity 100%. Further analysis revealed that its diagnostic value was better than CEA, CA19-9, CA72-4, alone or in combination. Moreover, the structure of serum microbiota was different in GC metastasis (GC-M) or non-metastasis (GC-NM).  

Interpretation: As a pilot investigation to characterize serum microbiome in GC, our study provided a novel strategy for discovering serum microbiota-targeted biomarkers for GC diagnosis.

Funding Statement: National Natural Science Foundation of China (81572070, 81601846, 81401709, 31471202). Natural Science Foundation of Shandong Province (ZR2017MH044). Taishan Scholars Program of Shandong Province (tshw20120206). Key Research and Development Project of Shandong Province (2016GSF201122, 2016GSF201124, 2016YYSP009, 2016GSF201120). The Fundamental Research Funds of Shandong University (2014QLKY03). Science and Technology Development Project in Jinan (201805084). Science Foundation of Qilu Hospital of Shandong University (2015QLQN38, 2015QLMS45). City of Weihai technique extension project (2016GNS023).

Declaration of Interests: The authors declare no conflict of interest.

Ethics Approval Statement: Our study was approved by the Ethics Committee of Qilu Hospital (KYLL-2015-097). The participants signed written informed consents.

Keywords: Gastric Cancer; Serum; Biomarker; Diagnosis; Microbiome

Suggested Citation

Dong, Zhao-Gang and Chen, Bin and Wang, Ding and Pan, Hong-wei and Liu, Min and Yang, Yong-mei and Zou, Ming-jin and Yang, Jun-jie and Xiao, Ke and Zhao, Rui and Zheng, Xin and Zhang, Lei and Zhang, Yi, Serum Microbiome Analysis as a Tool Towards Targeted Biomarker for Gastric Cancer (November 15, 2018). Available at SSRN: https://ssrn.com/abstract=3284853 or http://dx.doi.org/10.2139/ssrn.3284853

Zhao-Gang Dong (Contact Author)

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Bin Chen

Beihang University (BUAA) - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine

Beijing
China

Ding Wang

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Hong-wei Pan

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Min Liu

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Yong-mei Yang

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Ming-jin Zou

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Jun-jie Yang

Qilu Normal University - College of Life Science

Jinan, Shandong
China

Ke Xiao

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Rui Zhao

Shandong University - Department of Clinical Laboratory

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health

Jinan, Shandong
China

Xin Zheng

Shandong University - Department of Clinical Laboratory ( email )

Jinan, Shandong
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health ( email )

Jinan, Shandong
China

Lei Zhang

Beihang University (BUAA) - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine ( email )

Beijing
China

Yi Zhang

Shandong University - Department of Clinical Laboratory ( email )

Jinan, Shandong
China

Shandong Provincial Medicine and Health - Key Laboratory of Tumor Marker Translational Medicine ( email )

Jinan
China

Shandong University - Shandong Province Key Laboratories of Medicine and Health ( email )

Jinan, Shandong
China

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