RRC ID 65459
Author Katsurahara K, Shiozaki A, Kosuga T, Shimizu H, Kudou M, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Otsuji E.
Title ANO9 regulates PD-L2 expression and binding ability to PD-1 in gastric cancer.
Journal Cancer Sci
Abstract The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty-four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD-L2 via interferon (IFN)-related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD-1 by downregulating the expression of PD-L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD-L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD-L2 and binding ability to PD-1 via IFN-related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC.
Volume 112(3)
Pages 1026-1037
Published 2021-3-1
DOI 10.1111/cas.14796
PMID 33404124
PMC PMC7935785
MeSH Aged Anoctamins / antagonists & inhibitors Anoctamins / genetics Anoctamins / metabolism* Apoptosis / drug effects Apoptosis / genetics Apoptosis / immunology Biomarkers, Tumor / antagonists & inhibitors Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics Female Follow-Up Studies Gastrectomy Gene Expression Regulation, Neoplastic / drug effects Gene Knockdown Techniques Humans Immune Checkpoint Inhibitors / pharmacology Immune Checkpoint Inhibitors / therapeutic use Interferons / metabolism Male Phospholipid Transfer Proteins / antagonists & inhibitors Phospholipid Transfer Proteins / genetics Phospholipid Transfer Proteins / metabolism* Prognosis Programmed Cell Death 1 Ligand 2 Protein / genetics* Programmed Cell Death 1 Receptor / metabolism Stomach / pathology Stomach / surgery Stomach Neoplasms / genetics* Stomach Neoplasms / immunology Stomach Neoplasms / mortality Stomach Neoplasms / therapy Survival Rate
IF 4.966
Human and Animal Cells MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) HGC-27(RCB0500) NUGC-4(RCB1939)