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Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma

Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47‐SIRPα pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expressi...

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Autores principales: Koga, Naomichi, Hu, Qingjiang, Sakai, Akihiro, Takada, Kazuki, Nakanishi, Ryota, Hisamatsu, Yuichi, Ando, Koji, Kimura, Yasue, Oki, Eiji, Oda, Yoshinao, Mori, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353899/
https://www.ncbi.nlm.nih.gov/pubmed/34009732
http://dx.doi.org/10.1111/cas.14971
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author Koga, Naomichi
Hu, Qingjiang
Sakai, Akihiro
Takada, Kazuki
Nakanishi, Ryota
Hisamatsu, Yuichi
Ando, Koji
Kimura, Yasue
Oki, Eiji
Oda, Yoshinao
Mori, Masaki
author_facet Koga, Naomichi
Hu, Qingjiang
Sakai, Akihiro
Takada, Kazuki
Nakanishi, Ryota
Hisamatsu, Yuichi
Ando, Koji
Kimura, Yasue
Oki, Eiji
Oda, Yoshinao
Mori, Masaki
author_sort Koga, Naomichi
collection PubMed
description Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47‐SIRPα pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRPα expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRPα expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death‐ligand 1 (PD‐L1). Overall survival was significantly poorer with high SIRPα expression than with low expression in both TCGA and our patient cohort (P < .001 and P = .027, respectively). High SIRPα expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRPα was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8(+) T cells, and PD‐L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRPα/PD‐L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRPα indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD‐1‐PD‐L1 blockade.
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spelling pubmed-83538992021-08-15 Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma Koga, Naomichi Hu, Qingjiang Sakai, Akihiro Takada, Kazuki Nakanishi, Ryota Hisamatsu, Yuichi Ando, Koji Kimura, Yasue Oki, Eiji Oda, Yoshinao Mori, Masaki Cancer Sci Original Articles Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47‐SIRPα pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRPα expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRPα expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death‐ligand 1 (PD‐L1). Overall survival was significantly poorer with high SIRPα expression than with low expression in both TCGA and our patient cohort (P < .001 and P = .027, respectively). High SIRPα expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRPα was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8(+) T cells, and PD‐L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRPα/PD‐L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRPα indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD‐1‐PD‐L1 blockade. John Wiley and Sons Inc. 2021-06-11 2021-08 /pmc/articles/PMC8353899/ /pubmed/34009732 http://dx.doi.org/10.1111/cas.14971 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Koga, Naomichi
Hu, Qingjiang
Sakai, Akihiro
Takada, Kazuki
Nakanishi, Ryota
Hisamatsu, Yuichi
Ando, Koji
Kimura, Yasue
Oki, Eiji
Oda, Yoshinao
Mori, Masaki
Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title_full Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title_fullStr Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title_full_unstemmed Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title_short Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma
title_sort clinical significance of signal regulatory protein alpha (sirpα) expression in esophageal squamous cell carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353899/
https://www.ncbi.nlm.nih.gov/pubmed/34009732
http://dx.doi.org/10.1111/cas.14971
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