Frontiers in Immunology (Sep 2024)

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

  • Kuan Shen,
  • Kuan Shen,
  • Chuming Zhu,
  • Chuming Zhu,
  • Jianjun Wu,
  • Jianjun Wu,
  • Jiang Yan,
  • Jiang Yan,
  • Pengyu Li,
  • Shuqing Cao,
  • Xinyi Zhou,
  • Guozhong Yao

DOI
https://doi.org/10.3389/fimmu.2024.1430352
Journal volume & issue
Vol. 15

Abstract

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BackgroundThe interplay between colon adenocarcinoma (COAD) and branched-chain amino acid (BCAA) metabolism is not fully understood, presenting a crucial area for investigation.MethodsWe 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.ResultsOur 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.ConclusionThe 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.

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