A Combination of Methylation and Protein Markers is Capable of Detecting Gastric Cancer Detection by Combined Markers

Abstract

Aim: This study aimed to validate a combination of mSEPT9, mRNF180 and CA724 for gastric cancer (GC) detection. Patients & methods: The performance of mSEPT9, mRNF180 and CA724 was examined in a prospective cohort study with 518 participants (151 with GC, 56 with atrophic gastritis, 87 with other gastrointestinal diseases and 224 with no evidence of disease). Results:mSEPT9, mRNF180 or CA724 alone detected 48.3, 37.1 and 43.1% of GC, respectively. The combination of mSEPT9 and mRNF180 detected 60.3% of GC, and the combination of all three markers detected 68.6% of GC. The detection sensitivity of mSEPT9 and mRNF180 was significantly higher for gastric body and in elder subjects. mSEPT9 was correlated with poorer GC survival. Conclusion: The combination of mSEPT9, mRNF180 and CA724 was adequately sensitive for GC detection. The blood mSEPT9 was predictive for GC prognosis.

Lay abstract

Gastric cancer is the most common cancer type in the digestive system. In this study we developed an effective and convenient blood-based test to detect gastric cancer. This test combined a conventional protein test with a newly invented methylation test. We aimed to validate the test and examine its performance using a prospective cohort study. The study showed that the test has promising potential for noninvasive early detection of gastric cancer. We found that single protein or methylation markers detected a proportion of gastric cancer cases, while a combination of these markers exhibited maximal detection capability. Therefore we concluded that the combined test provided adequate efficacy and should be used as a strategy for future gastric cancer detection.

Keywords::

• CA724
• colorectal cancer
• gastric cancer
• methylation
• RNF180
• SEPT9
• septin9

Author contributions

J Xu, J Guo and X Yang designed the study. J Xu, Jianlin S, T Wang, W Zhu, L Zuo and J Hao recruited the subjects. J Xu and J Song collected the samples and liaised with the laboratory. J Xu analyzed the data, made the figures and tables and wrote the manuscript. J Guo and X Yang proofread the manuscript. X Yang submitted the manuscript.

Financial & competing interests disclosure

This study was supported by Yunnan Health Training Special Project of High Level Talents (grant no.: D-2017032). This study was also funded by the Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province (2021LCZXXF-XH04) of (2X2019-01-02). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Approval was granted for the study by the ethics committees of the First People’s Hospital of Yunnan Province (approval no. KHLL 2019-034). In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Availability of data & materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by Yunnan Health Training Special Project of High Level Talents (grant no.: D-2017032). This study was also funded by the Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province (2021LCZXXF-XH04) of (2X2019-01-02). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.