Identification of a Biomarker Combination for Survival Stratification in pStage II/III Gastric Cancer after Curative Resection

Itaru Hashimoto; Yayoi Kimura; Naohide Oue; Yukihiko Hiroshima; Toru Aoyama; Yasushi Rino; Tomoyuki Yokose; Wataru Yasui; Yohei Miyagi; Takashi Oshima

doi:10.3390/cancers14184427

Cancers (Sep 2022)

Identification of a Biomarker Combination for Survival Stratification in pStage II/III Gastric Cancer after Curative Resection

Itaru Hashimoto,
Yayoi Kimura,
Naohide Oue,
Yukihiko Hiroshima,
Toru Aoyama,
Yasushi Rino,
Tomoyuki Yokose,
Wataru Yasui,
Yohei Miyagi,
Takashi Oshima

Affiliations

Itaru Hashimoto: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
Yayoi Kimura: Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Naohide Oue: Department of Molecular Pathology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima 734-8551, Japan
Yukihiko Hiroshima: Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
Toru Aoyama: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Yasushi Rino: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Tomoyuki Yokose: Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
Wataru Yasui: Department of Molecular Pathology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima 734-8551, Japan
Yohei Miyagi: Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
Takashi Oshima: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan

DOI: https://doi.org/10.3390/cancers14184427
Journal volume & issue: Vol. 14, no. 18
p. 4427

Abstract

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Background: We sought to identify an optimal combination of survival risk stratification markers in patients with pathological (p) stage II/III gastric cancer (GC) after curative resection. Methods: We measured the expression levels of 127 genes in pStage II/III GC tissues of two patient cohorts by quantitative polymerase chain reaction (qPCR) and the expression of 1756 proteins between two prognosis (good and poor) groups by proteomic analysis to identify candidate survival stratification markers. Further, immunohistochemistry (IHC) using tumor microarrays (TMAs) in another cohort of patients was performed to identify an optimal biomarker combination for survival stratification in GC patients. Results: secreted protein acidic and rich in cysteine (SPARC), erb-b2 receptor tyrosine kinase 2 (ERBB2), inhibin subunit beta A (INHBA), matrix metallopeptidase-11 (MMP11), tumor protein p53 (TP53), and platelet-derived growth factor receptor-beta (PDGFRB) were identified as candidate biomarkers from qPCR analysis, and SPARC and galectin-10 were obtained from the proteomic analysis. The combination of PDGFRB, INHBA, MMP11, and galectin-10 was identified as the optimal combination of survival risk stratification markers. Conclusions: A combination of four proteins in GC tissues may serve as useful survival risk stratification markers in patients with pStage II/III GC following curative resection. Our results may facilitate future multicenter prospective clinical trials.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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