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Genetics and Genomics

A liquid biopsy signature for predicting early recurrence in patients with gastric cancer

British Journal of Cancer volume 128, pages 1105–1116 (2023)Cite this article

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Abstract

Background

Gastric cancer (GC) patients who experience recurrence within the first year following surgery (early recurrence [ER]) exhibit worse prognosis. Herein, we established a microRNA-based liquid biopsy assay to predict ER in GC patients.

Methods

A comprehensive biomarker discovery was performed by analysing miRNA expression profiling in 271 primary GC tumours. Thereafter, the expression of these biomarkers was validated in 290 GC cases, which included 218 tissues and 72 pre-treatment sera, from two independent institutions.

Results

A panel of 8 miRNAs was identified during the initial biomarker discovery, and this panel could robustly predict ER in a tissue-based clinical cohort (area under the curve [AUC]: 0.81). Furthermore, a model combining the miRNA panel, microsatellite instability (MSI) status and tumour size exhibited superior predictive performance (AUC: 0.86), and was defined as a Prediction of Early Recurrence in GC (PERGC) signature, which was successfully validated in another independent cohort (AUC: 0.82). Finally, the PERGC signature was translated into a liquid biopsy assay (AUC: 0.81), and a multivariate regression analysis revealed this signature to be an independent predictor for ER (odds ratio: 11.20).

Conclusion

We successfully established a miRNA-based liquid biopsy signature that robustly predicts the risk of ER in GC patients.

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Fig. 1: Survival outcomes of stage II/III gastric cancer patients with early recurrence in two independent public data sets.
Fig. 2: Biomarker discovery phase of candidate miRNAs to predict early recurrence in primary tumours from gastric cancer patients.
Fig. 3: Clinical training phase of the PERGC signature for predicting the early recurrence in tissue specimens from stage II/III GC patients.
Fig. 4: Clinical validation phase for the PERGC signature in predicting early recurrence in tissue specimens from stage II/III GC patients.
Fig. 5: Clinical performance evaluation phase for the PERGC model as a liquid biopsy assay for predicting early recurrence in pre-surgery serum specimens from stage II/III GC patients.

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Data availability

The data sets analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Dr. Kota Nakamura, Dr. Katsuki Miyazaki, Dr. Silei Sui, Dr. Caiming Xu, Dr. Hiroyuki Hanayama, Dr. Milad Moloudizargari and Dr. Nour-Lynn Mouallem for their thoughtful discussions and advice during the course of this project.

Funding

This work was supported by the CA072851, CA181572, and CA187956 grants from the National Cancer Institute, National Institutes of Health, and a generous pilot grant from the Stupid Strong Foundation.

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Authors and Affiliations

  1. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA, USA

    Keisuke Okuno, Souvick Roy & Ajay Goel

  2. Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan

    Keisuke Okuno, Masanori Tokunaga & Yusuke Kinugasa

  3. Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan

    Shuichi Watanabe

  4. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Mitsuro Kanda & Yasuhiro Kodera

  5. City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Ajay Goel

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  1. Keisuke Okuno
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Contributions

Study concept and design (KO, SW, MT, Y Kinugasa, AG); provision of samples (KO, MK, MT, Y Kodera, Y Kinugasa); acquisition of clinical data (KO, MK, MT, Y Kodera, Y Kinugasa, AG); analysis and interpretation of data (KO, SW, SR, AG); statistical analysis (KO, SW, SR, AG); drafting of the manuscript (KO, SW, SR, MK, MT, Y Kodera, Y Kinugasa, AG).

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Correspondence to Ajay Goel.

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The authors declare no competing interests.

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A written informed consent was obtained from all patients who enrolled at the present study. The study was conducted in compliance with the Declaration of Helsinki and was approved by the Institutional Review Boards of all participating institutions.

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Okuno, K., Watanabe, S., Roy, S. et al. A liquid biopsy signature for predicting early recurrence in patients with gastric cancer. Br J Cancer 128, 1105–1116 (2023). https://doi.org/10.1038/s41416-022-02138-1

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