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ANO9 regulates PD-L2 expression and binding ability to PD-1 in gastric cancer
Keita Katsurahara1, Atsushi Shiozaki1, Toshiyuki Kosuga1
1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
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.
Insights
Annovon (ANO9) protein regulates PD-L2 expression and PD-1 binding in gastric cancer (GC). High ANO9 levels indicate a poor prognosis, suggesting ANO9 as a potential biomarker and therapeutic target for immune checkpoint blockage in GC.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The role of Annovon (ANO9) in gastrointestinal cancer is not well understood.
- Investigating ANO9's function is crucial for understanding gastric cancer (GC) progression.
Purpose of the Study:
- To elucidate the biological behaviors of ANO9 in gastric cancer.
- To determine the clinical prognostic value of ANO9 in advanced GC patients.
Main Methods:
- ANO9 knockdown in human GC cell lines (MKN7, MKN74) using siRNA.
- Immunohistochemical (IHC) analysis of 84 advanced GC tissue samples.
- Microarray analysis and flow cytometry to assess gene regulation and protein interactions.
Main Results:
- ANO9 knockdown inhibited cancer cell progression in MKN7 and MKN74 cells.
- ANO9 was found to regulate PD-L2 expression through interferon (IFN)-related genes.
- ANO9 depletion reduced PD-L2 expression and PD-1 binding.
- Strong ANO9 expression correlated with PD-L2 and served as an independent poor prognostic factor in advanced GC.
Conclusions:
- ANO9 regulates PD-L2 and PD-1 binding via IFN-related genes in gastric cancer.
- ANO9 shows potential as a prognostic biomarker for GC.
- ANO9 may be a viable therapeutic target for immune checkpoint blockage (ICB) in GC.
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