TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer.

Autor:	Galbraith NJ; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom. Electronic address: norman.galbraith@glasgow.ac.uk., Quinn JA; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Al-Badran SS; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Pennel KAF; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Hillson LVS; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Hatthakarnkul P; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., McKenzie M; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Maka N; Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom., Loi L; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Frixou M; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom., Steele CW; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom., Roxburgh CS; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom., Horgan PG; Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom., McMillan DC; Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom., Edwards J; School of Cancer Sciences, Wolfson-Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2024 Oct; Vol. 48, pp. 102064. Date of Electronic Publication: 2024 Jul 27.
DOI:	10.1016/j.tranon.2024.102064
Abstrakt:	Background: Transforming growth factor β-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer. Methods: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens. Expression levels of cytoplasmic TAK1 by QuPath digital quantification and punctate TAK1 staining was scored using a manual point scoring technique and correlated with clinicopathological features, immune checkpoint expression and cancer-specific survival. Bulk RNA sequencing was performed in specimens to determine mutational profiles and differentially expressed genes. Results: A cohort of 875 patients who had undergone colorectal cancer resection were assessed for TAK1 expression. Higher levels of cytoplasmic TAK1 expression correlated with elevated PD1 and PD-L1 expression (p < 0.010). High punctate TAK1 expression was more commonly identified in poorly differentiated colorectal cancers (p = 0.036), had dysregulated mutational and transcriptional profiles with decreased insulin-like growth factor 2(IGF2) expression (p < 0.010), and independently predicted poor cancer-specific survival (HR 2.690, 95% CI 1.419-5.100, p = 0.002). The association of punctate TAK1 expression and recurrence remained after subgroup analysis for microsatellite-stable colorectal cancer (p = 0.028). Discussion: Punctate TAK1 expression is associated with worse cancer specific survival. TAK1 signalling may be an important pathway to investigate underlying mechanisms for recurrence in microsatellite-stable colorectal cancer. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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