GPR155 Serves as a Predictive Biomarker for Hematogenous Metastasis in Patients with Gastric Cancer

Shimizu, Dai; Kanda, Mitsuro; Tanaka, Haruyoshi; Kobayashi, Daisuke; Tanaka, Chie; Hayashi, Masamichi; Iwata, Nakao; Niwa, Yasumasa; Takami, Hideki; Yamada, Suguru; Fujii, Tsutomu; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

doi:10.1038/srep42089

Cited by 31 publications

(22 citation statements)

References 51 publications

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“…Analysis of 84 mRNAs associated with cancer was performed using RT2 Profiler PCR Arrays (Qiagen, Hilden, Germany) . The levels of candidate metastasis‐specific mRNAs were determined in 14 cell lines and in knockout (KO) cells.…”

Section: Methodsmentioning

confidence: 99%

“…Analysis of 84 mRNAs associated with cancer was performed using RT2 Profiler PCR Arrays (Qiagen, Hilden, Germany). 17 The levels of candidate metastasis-specific mRNAs were determined in 14 cell lines and in knockout (KO) cells. Analysis of cancer pathway-specific protein expression was conducted using a PathScan Intracellular Signaling Array Kit and a PathScan Cancer Phenotype Antibody Array Kit (CST).…”

Section: Pathway Analysismentioning

confidence: 99%

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Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer

Umeda

Kanda

Miwa

et al. 2019

Intl Journal of Cancer

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Liver metastasis is often fatal in patients with gastric cancer, therefore, we aimed to identify genes associated with the mechanisms of liver metastasis of gastric cancer (GC) and to investigate their potential to predict recurrence and to serve as targets of therapy. Recurrence pattern‐specific transcriptome analysis was performed to identify liver metastasis‐associated genes. A stable knockout cell line was generated to investigate metabolic pathways that contribute to the malignant phenotype in vitro and vivo. Three hundred GC patients were analyzed to demonstrate an association between gene expression levels and clinicopathological parameters. As a results extracellular matrix complex subunit 1 (FRAS1) was identified as a liver metastasis‐associated gene. Pathway analysis revealed that FRAS1 expression was significantly correlated with the expression of genes encoding TGFB1, MAP1B, AHNAK, BMP2, MUC1, BIRC5, MET, CDH1, RB1 and MKI67. FRAS1 expression was associated with the activation of the EGFR and PI3K signaling pathways. The proliferation ability of FRAS1 knockout cell line (FRAS1‐KO) was inhibited compared to that of the parent cell line through caspase activity increment and cell cycle alteration. FRAS1‐KO cells exhibited increased responsiveness to oxygen stress and diminished stemness, invasiveness, and migration. Mouse models of GC revealed decreases in tumor formation and generation of metastasis by FRAS1‐KO cells. Moreover, the cumulative liver recurrence rate was significantly increased in patients with GC with high FRAS1 expression levels. We concluded that FRAS1 contributes to the malignant phenotype of GC, especially liver metastasis, and may therefore serve as a predictive marker or a target for treating liver metastasis.

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Section: Methodsmentioning

confidence: 99%

Section: Pathway Analysismentioning

confidence: 99%

Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer

Umeda

Kanda

Miwa

et al. 2019

Intl Journal of Cancer

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“…The samples were tested in triplicate, and samples without a template were included in each PCR plate as a negative control (21). Real-time SYBR Green fluorescence was detected using an ABI StepOnePlus Real-Time PCR System (Applied Biosystems; Thermo Fisher Scientific, Inc.) (22) and the 2 -ΔΔCq method was used for PCR quantification (23). The expression level of each sample is expressed as the value of the CPNE5 amplicon divided by that of GAPDH.…”

Section: Methodsmentioning

confidence: 99%

Copine�5 expression predicts prognosis following curative resection of esophageal squamous cell carcinoma

et al. 2018

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Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Identification of biomarkers to accurately predict the risk of recurrence and survival following curative esophageal resection is required to improve patient outcomes. The copine 5 (CPNE5) gene encodes a calcium-dependent lipid-binding intracellular protein. Copine proteins interact with diverse target proteins that are components of pathways that aberrantly regulate the phenotypes of malignant cells. However, limited information is available on the role of CPNE5 in cancer. The present study investigated whether CPNE5 may serve as a predictive marker of the prognosis of patients with ESCC following curative resection. CPNE5 mRNA expression levels and the methylation status of the CPNE5 promotor region were measured in 11 ESCC cell lines. CPNE5 mRNA expression levels in 106 pairs of surgically resected specimens were measured, and their associations with clinicopathological characteristics were analyzed. The CPNE5 mRNA expression levels in 9 ESCC cell lines were decreased compared with those of the non-tumorigenic esophageal mucosa cell line Het-1A. Bisulfite sequencing detected the methylation of the CPNE5 promotor region in all cell lines tested, including Het-1A. Furthermore, analysis of tissues revealed that CPNE5 mRNA expression was significantly lower in ESCC cells compared with cognate non-cancerous adjacent mucosal cells. Kaplan-Meier analysis revealed that patients with low CPNE5 expression experienced significantly shorter overall survival. Multivariable analysis identified low CPNE5 expression to be an independent prognostic factor of OS. Analysis of recurrence patterns revealed that significantly more patients with local recurrence expressed lower levels of CPNE5 mRNA. These findings indicated that CPNE5 expression in ESCC tissues may serve as an informative biomarker for predicting ESCC recurrence, particularly in patients with local recurrence, and may help to ensure that patients receive optimal treatment and follow-up.

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“…Given that, it is worth challenging to develop a dual-marker expression panel being simple and consisted of only two markers, but having a high predictive performance. Since 2014, researchers at Nagoya University discovered 15 prognostic biomarkers for gastric cancer [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. This study aimed at testing the hypothesis that a combination of molecular markers can be used to establish a dual-marker expression panel that will improve stratification of patients with gastric cancer.…”

Section: Original Researchmentioning

confidence: 99%

A novel dual‐marker expression panel for easy and accurate risk stratification of patients with gastric cancer

et al. 2018

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Development of specific biomarkers is necessary for individualized management of patients with gastric cancer. The aim of this study was to design a simple expression panel comprising novel molecular markers for precise risk stratification. Patients (n = 200) who underwent gastrectomy for gastric cancer were randomly assigned into learning and validation sets. Tissue mRNA expression levels of 15 candidate molecular markers were determined using quantitative PCR analysis. A dual‐marker expression panel was created according to concordance index (C‐index) values of overall survival for all 105 combinations of two markers in the learning set. The reproducibility and clinical significance of the dual‐marker expression panel were evaluated in the validation set. The patient characteristics of the learning and validation sets were well balanced. The C‐index values of combinations were significantly higher compared with those of single markers. The panel with the highest C‐index (0.718) of the learning set comprised SYT8 and MAGED2, which clearly stratified patients into low‐, intermediate‐, and high‐risk groups. The reproducibility of the panel was demonstrated in the validation set. High expression scores were significantly associated with larger tumor size, vascular invasion, lymph node metastasis, peritoneal metastasis, and advanced disease. The dual‐marker expression panel provides a simple tool that clearly stratifies patients with gastric cancer into low‐, intermediate‐, and high risk after gastrectomy.

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GPR155 Serves as a Predictive Biomarker for Hematogenous Metastasis in Patients with Gastric Cancer

Cited by 31 publications

References 51 publications

Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer

Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer

Copine�5 expression predicts prognosis following curative resection of esophageal squamous cell carcinoma

A novel dual‐marker expression panel for easy and accurate risk stratification of patients with gastric cancer

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