Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer.


Journal

Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354

Informations de publication

Date de publication:
01 11 2021
Historique:
pubmed: 31 10 2019
medline: 23 11 2021
entrez: 31 10 2019
Statut: ppublish

Résumé

This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

Sections du résumé

OBJECTIVE
This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC).
SUMMARY BACKGROUND DATA
Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis.
METHODS
We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC.
RESULTS
Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively).
CONCLUSIONS
We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

Identifiants

pubmed: 31663973
pii: 00000658-202111000-00036
doi: 10.1097/SLA.0000000000003647
pmc: PMC7577555
mid: NIHMS1636561
doi:

Substances chimiques

Biomarkers, Tumor 0
MicroRNAs 0
RNA, Neoplasm 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e425-e434

Subventions

Organisme : NCI NIH HHS
ID : R01 CA202797
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA184792
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA187956
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA181572
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214254
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA072851
Pays : United States

Informations de copyright

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

The authors report no conflicts of interest to disclose.

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Auteurs

Tadanobu Shimura (T)

Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX.
Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA.

Shusuke Toden (S)

Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX.
Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA.

Raju Kandimalla (R)

Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX.
Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA.

Yuji Toiyama (Y)

Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.

Yoshinaga Okugawa (Y)

Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.

Mitsuro Kanda (M)

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

Hideo Baba (H)

Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.

Yasuhiro Kodera (Y)

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

Masato Kusunoki (M)

Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.

Ajay Goel (A)

Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX.
Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA.

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