Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population

Jimmy Bok Yan So, Ritika Kapoor, Feng Zhu, Calvin Koh, Lihan Zhou, Ruiyang Zou, Yew Chung Tang, Patrick C.K. Goo, Sun Young Rha, Hyun Cheol Chung, Joanne Yoong, Celestial T. Yap, Jaideepraj Rao, Chung King Chia, Stephen Tsao, Asim Shabbir, Jonathan Lee, Kong Peng Lam, Mikael Hartman, Wei Peng YongHeng Phon Too, Khay Guan Yeoh

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14 Citations (Scopus)

Abstract

Objective An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population. Design We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared with Helicobacter pylori (HP) serology, serum pepsinogens (PGs), 'ABC' method, carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model. Results We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year). Conclusion We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer.

Original languageEnglish
Article number33028667
Pages (from-to)829-837
Number of pages9
JournalGut
Volume70
Issue number5
DOIs
Publication statusPublished - 2021 May 1

Bibliographical note

Funding Information:
Funding The Singapore Gastric Cancer Consortium (SGCC) is a national translational research group comprising clinicians and scientists working in gastric cancer research from academic medical centres, universities, hospitals and research institutes across Singapore. It receives funding from the National Research Foundation Singapore under its Translational and Clinical Research (TCR) Flagship Programme and Open Fund-Large Collaborative Grant (OF-LCG), administered by the Singapore Ministry of Health’s National Medical Research Council. This study was supported by the Bedside & Bench grant (NMRC/BnB/0014b/2014) and the Translational and Clinical Research grant administered by Singapore Ministry of Health’s National Medical Research Council (NMRC/TCR/009-NUHS/2013, NMRC/ TCR/001-NUS/2007) and RIE2020 Centre Grant (CG) Programme (NMRC/CG/ M005/2017_NCIS), as well as the COT and GAP grants administered by Singapore A*STAR Exploit Technology.

Funding Information:
Competing interests KGY, JBYS, WPY, HPT, LZ, RZ and FZ were coinventors in the patent application ’Serum MicroRNA Biomarker for the Diagnosis of Gastric Cancer’. HPT, LZ and RZ are founders and shareholders of MiRXES. LZ, RZ and YCT are employees of MiRXES. HCC received grants from Lilly, GSK, MSD. Merck-Serono, BMS-Ono, Taiho outside the submitted work. The rest of authors declare no competing interests.

Funding Information:
The Singapore Gastric Cancer Consortium (SGCC) is a national translational research group comprising clinicians and scientists working in gastric cancer research from academic medical centres, universities, hospitals and research institutes across Singapore. It receives funding from the National Research Foundation Singapore under its Translational and Clinical Research (TCR) Flagship Programme and Open Fund-Large Collaborative Grant (OF-LCG), administered by the Singapore Ministry of Health's National Medical Research Council. This study was supported by the Bedside & Bench grant (NMRC/BnB/0014b/2014) and the Translational and Clinical Research grant administered by Singapore Ministry of Health's National Medical Research Council (NMRC/TCR/009-NUHS/ 2013, NMRC/ TCR/001-NUS/ 2007) and RIE2020 Centre Grant (CG) Programme (NMRC/CG/ M005/2017-NCIS), as well as the COT and GAP grants administered by Singapore A?STAR Exploit Technology.

Publisher Copyright:
© 2021 Author(s).

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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