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. 2020 Nov;123(11):1656-1664.
doi: 10.1038/s41416-020-01063-5. Epub 2020 Sep 16.

Novel urinary protein biomarker panel for early diagnosis of gastric cancer

Takaya Shimura  1 , Delphine Dayde  2 , Hong Wang  3   4 , Yusuke Okuda  5 , Hiroyasu Iwasaki  5 , Masahide Ebi  5   6 , Mika Kitagawa  5 , Tamaki Yamada  7 , Tomonori Yamada  8 , Samir M Hanash  3 , Ayumu Taguchi  2   9   10 , Hiromi Kataoka  5
Affiliations

Novel urinary protein biomarker panel for early diagnosis of gastric cancer

Takaya Shimura et al. Br J Cancer. 2020 Nov.

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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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Study flowchart and quantitative mass spectrometry.
a Consort diagram; b Information on individual donor, sample pooling and TMT label; c High-throughput quantitative proteomics platform for cancer biomarker discovery; d Urinary protein with aberrant expression in gastric cancer patients. MS mass spectrometry, ELISA enzyme-linked immunosorbent assay, TMT tandem mass tag, GC gastric cancer, HC healthy control, IA + IB/Ctrl ratio of urinary protein in GC patients with stage IA or IB to that in HCs, II + III/Ctrl ratio of urinary protein in GC patients with stage II or III to that in HCs.
Fig. 2
Fig. 2. Receiver operating characteristic (ROC) curves.
a Training cohort, b Validation cohort. ROC curves were obtained from values normalised to urinary total protein.
Fig. 3
Fig. 3. Sex-specific urinary biomarker panels.
a Male cohort, b Female cohort. Subset analysis was performed according to sex. ROC curves were obtained from values normalised to urinary total protein.
Fig. 4
Fig. 4. Early detection of stage I GC.
a Whole cohort, b Male cohort, c Female cohort. ROC curves were obtained from values normalised to urinary total protein to distinguish stage I GC patients from healthy controls.
See this image and copyright information in PMC

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