Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study.

Autor:	Arai H; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.; Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan., Gandhi N; Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Caris Life Sciences, Phoenix, Arizona, USA., Battaglin F; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Wang J; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Algaze S; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Jayachandran P; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Soni S; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Zhang W; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Yang Y; Department of Population and Public Health Sciences, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Millstein J; Department of Population and Public Health Sciences, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Lo JH; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Sohal D; Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio, USA., Goldberg R; West Virginia University Cancer Institute, Morgantown, West Virginia, USA., Hall MJ; Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Scott AJ; Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona, USA., Hwang JJ; Department of Solid Tumor Oncology, GI Medical Oncology Levine Cancer Institute, Charlotte, North Carolina, USA., Lou E; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA., Weinberg BA; Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA., Marshall J; Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA., Goel S; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA., Xiu J; Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Caris Life Sciences, Phoenix, Arizona, USA., Korn WM; Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Caris Life Sciences, Phoenix, Arizona, USA., Lenz HJ; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA lenz@usc.edu.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Nov 05; Vol. 12 (11). Date of Electronic Publication: 2024 Nov 05.
DOI:	10.1136/jitc-2024-010326
Abstrakt:	Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages. This large-scale study comprehensively examined the molecular significance of CD47 gene expression in CRC. Methods: We analyzed the next-generation sequencing data of DNA and RNA from 14,287 CRC cases included in the data set of a commercial Clinical Laboratory Improvement Amendments-certified laboratory (Caris Life Sciences). The cases were divided into two groups based on the median value of CD47 gene expression levels. The molecular and immune profiles between the groups were compared, and the relationship between CD47 expression and survival outcomes was further examined. Results: In CD47 -high tumors, the proportion of consensus molecular subtypes 1 and 4 was significantly higher than in CD47 -low tumors. The expression levels of damage-associated molecular pattern-related genes showed a positive correlation with CD47 expression levels. Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, and transforming growth factor beta, were significantly activated in CD47 -high tumors. Additionally, the expression levels of a panel of adaptive immune checkpoint genes and estimates of immune cells constituting the tumor microenvironment (TME) were significantly higher in CD47 -high tumors. Conclusions: CD47 expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC. Competing Interests: Competing interests: NG, JX, and WMK are employees of Caris Life Sciences. All remaining authors have declared no conflicts of interest. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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