GPR155 Serves as a Predictive Biomarker for Hematogenous Metastasis in Patients with Gastric Cancer.
The prognosis of patients with gastric cancer (GC) with hematogenous metastasis is dismal. Identification of biomarkers specific for hematogenous metastasis is required to develop personalized treatments that improve patients' outcomes. Global expression profiling of GC tissues with synchronous hepatic metastasis without metastasis to the peritoneal cavity or distant lymph nodes was conducted using next-generation sequencing and identified the G protein-coupled receptor 155 (GPR155) as a candidate biomarker. GPR155 transcription was suppressed in GC cell lines compared with a nontumorigenic cell line. DNA methylation of the GPR155 promoter region was not detected, albeit 20% of GC cell lines harbored copy number loss at GPR155 locus. The expression levels of GPR155 mRNA correlated inversely with those of TWIST1 and WNT5B. Inhibition of GPR155 expression increased the levels of p-ERK1/2 and p-STAT1, significantly increased cell proliferation, and increased the invasiveness of a GC cell lines. GPR155 mRNA levels in GC clinical samples correlated with hematogenous metastasis and recurrence. Multivariate analysis revealed that reduced expression of GPR155 mRNA was an independent predictive marker of hematogenous metastasis. GPR155 may represent a biomarker for diagnosing and predicting hematogenous metastasis of GC.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Dai
D
Shimizu
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mitsuro
M
Kanda
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Haruyoshi
H
Tanaka
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Daisuke
D
Kobayashi
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Chie
C
Tanaka
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Masamichi
M
Hayashi
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Naoki
N
Iwata
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yukiko
Y
Niwa
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hideki
H
Takami
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Suguru
S
Yamada
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Tsutomu
T
Fujii
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Goro
G
Nakayama
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Michitaka
M
Fujiwara
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yasuhiro
Y
Kodera
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059467:Transcriptome
D014408:Biomarkers, Tumor; C000627431:GPR155 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled