Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression.

Autor:	Shen K; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China.; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Zhu C; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China.; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Wu J; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China.; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Yan J; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China.; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Li P; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Cao S; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Zhou X; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Yao G; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 02; Vol. 15, pp. 1430352. Date of Electronic Publication: 2024 Sep 02 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1430352
Abstrakt:	Background: The interplay between colon adenocarcinoma (COAD) and branched-chain amino acid (BCAA) metabolism is not fully understood, presenting a crucial area for investigation. Methods: We developed a prognostic model based on BCAA metabolism using the least absolute shrinkage and selection operator (LASSO) regression algorithm. We employed qRT-PCR and Western blot analyses to examine NOTCH3 expression in COAD tissues versus adjacent non-cancerous tissues and various cell lines. We also investigated the impact of NOTCH3 on COAD cell proliferation, invasion, and migration through in vitro and in vivo experiments. Results: Our BCAA metabolism-related signature (BRS) distinguished between different immune features, tumor mutation burdens, responses to immunotherapy, and drug sensitivity among COAD patients. NOTCH3 was found to be overexpressed in COAD, promoting tumor growth as verified through various assays. The model effectively predicted COAD prognosis and patient responses to treatments, underscoring the potential of BCAA pathways as therapeutic targets. Conclusion: The BRS is instrumental in predicting the prognosis and therapeutic response in COAD, with NOTCH3 playing a significant role in the proliferation, invasion and migration of COAD. These findings suggest that targeting BCAA metabolism and NOTCH3 could advance COAD treatment strategies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Shen, Zhu, Wu, Yan, Li, Cao, Zhou and Yao.)
Databáze:	MEDLINE
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