Molecular Diagnostics

Novel urinary protein biomarker panel for early diagnosis of gastric cancer

Abstract

Background

With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC).

Methods

Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort.

Results

Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females).

Conclusions

Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.

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Fig. 1: Study flowchart and quantitative mass spectrometry.
Fig. 2: Receiver operating characteristic (ROC) curves.
Fig. 3: Sex-specific urinary biomarker panels.
Fig. 4: Early detection of stage I GC.

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Acknowledgements

We wish to thank Yukimi Hashidume-Itoh for handling urine samples and Takako Onodera for data management of patients enrolled in this study (Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences). We are grateful to our clinical colleagues who assisted in sample collection.

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Affiliations

Authors

Contributions

Study concept and design: T.S. Acquisition of data: T.S., D.D., H.W., Y.O., H.I., M.E., M.K., T.Y. and T.Y. Analysis and interpretation of data: T.S., D.D., H.W. and A.T. Drafting of the manuscript: T.S. Critical revision for important intellectual content: H.W. and A.T. Statistical analysis: T.S. Obtained funding: T.S. Administrative, technical or material support: D.D., H.W. and A.T. Study supervision: S.M.H. and H.K.

Corresponding author

Correspondence to Takaya Shimura.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the ethics committee at each participating institution (Institutional Review Board at Nagoya City University Hospital, Institutional Review Board at Nagoya Daini Red Cross Hospital and Ethical Committee at Okazaki Public Health Center), and was conducted according to the ethical guidelines of the Helsinki Declaration of 1964 and later versions. All patients provided written, informed consent prior to enrolment in the study.

Data availability

The data that support the findings of this study are available on request from the corresponding author (T.S.).

Competing interests

The authors declare no competing interests.

Funding information

This study was supported, in part, by Japan Agency for Medical Research and Development under Grant Number JP19lm0203005j0003 (to T.S.) and the Takeda Science Foundation (to T.S.).

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Shimura, T., Dayde, D., Wang, H. et al. Novel urinary protein biomarker panel for early diagnosis of gastric cancer. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-01063-5

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