Open AccessANO9 regulates PD‐L2 expression and binding ability to PD‐1 in gastric cancer
Author(s) -
Katsurahara Keita,
Shiozaki Atsushi,
Kosuga Toshiyuki,
Shimizu Hiroki,
Kudou Michihiro,
Arita Tomohiro,
Konishi Hirotaka,
Komatsu Shuhei,
Kubota Takeshi,
Fujiwara Hitoshi,
Okamoto Kazuma,
Kishimoto Mitsuo,
Konishi Eiichi,
Otsuji Eigo
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14796
Subject(s) - gene knockdown , flow cytometry , immunohistochemistry , cancer research , pd l1 , cancer , microarray analysis techniques , biomarker , immune system , biology , apoptosis , cancer cell , gene , immunotherapy , gene expression , microbiology and biotechnology , immunology , genetics
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.