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

Sep 21, 2026

Uploaded by Levi

Colon adenocarcinoma (COAD) progression is linked to branched-chain amino acid (BCAA) metabolism, yet the underlying connections to immune features and actionable targets remain insufficiently clarified. This study builds a prognostic model using a BCAA metabolism-related signature derived from LASSO regression and evaluates its performance across patient subgroups. NOTCH3 expression is measured in COAD tissues versus adjacent non-cancer tissues and multiple cell lines via qRT-PCR and Western blot. Functional experiments assess how NOTCH3 influences COAD proliferation, invasion, and migration in vitro and in vivo, while results support BCAA pathways as therapeutic targets.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background

Methods

Results

Conclusion

Keywords

TYPE Original Research PUBLISHED 02 September 2024 DOI 10.3389/fimmu.2024.1430352 OPEN ACCESS EDITED BY Youqiong Ye, Shanghai Jiao Tong University, China REVIEWED BY Tao Wu, Shanghai University of Traditional Chinese Medicine, China Jingjing Qi, Shanghai Jiao Tong University, China *CORRESPONDENCE Guozhong Yao [yaoguozhong133@163.com](yaoguozhong133@163.com) †These authors have contributed equally to this work RECEIVED 09 May 2024 ACCEPTED 07 August 2024 PUBLISHED 02 September 2024 CITATION Shen K, Zhu C, Wu J, Yan J, Li P, Cao S, Zhou X and Yao G (2024) Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression. Front. Immunol. 15:1430352 . doi: 10.3389/fimmu.2024.1430352 COPYRIGHT © 2024 Shen, Zhu, Wu, Yan, Li, Cao, Zhou and Yao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression Kuan Shen 1,2†, Chuming Zhu 1,2†, Jianjun Wu 1,2†, Jiang Yan 1,2†, Pengyu Li 2, Shuqing Cao 2, Xinyi Zhou 2 and Guozhong Yao 1* 1 Department of General Surgery, Liyang People ’s Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, China, 2 Department of General Surgery, the First Afﬁliated Hospital of Nanjing Medical University, Nanjing, China 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, promotingtumor growth asveriﬁedthroughvarious 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, Abbreviations: COAD, Colon Adenocarcinoma; BCAA, Branched-Chain Amino Acids; LASSO, Least Absolute Shrinkage and Selection Operator; qRT-PCR, Quantitative Reverse Transcription Polymerase Chain Reaction; BRS, BCAA Metabolism-Related Signature; TISCH2, Tumor Immune Single Cell Hub 2; ssGSEA, Single-Sample Gene Set Enrichment Analysis; TME, Tumor Microenvironment; TMB, Tumor Mutational Burden; IC50, Half-Maximal Inhibitory Concentration; AUC, Area Under the Curve; KM, Kaplan-Meier; TCGA, The Cancer Genome Atlas; GEO, Gene Expression Omnibus; HE, Hematoxylin and Eosin; TIP, Tracking Tumor Immunophenotype; CTLA4, Cytotoxic T-Lymphocyte Associated Protein 4; PD1, Programmed Cell Death Protein 1; APC, Antigen-Presenting Cell; MDSC, Myeloid-Derived Suppressor Cells; ROC, Receiver Operating Characteristic; OS, Overall Survival; DSS, Disease-Speciﬁc Survival; PFI, Progression-Free Interval. Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) invasion and

FAQs

What is the main research focus of this study?

The study focuses on exploiting BCAA metabolism and NOTCH3 expression to predict and target colorectal cancer progression, particularly COAD.

How is the prognostic model constructed?

A prognostic model is developed using a BCAA metabolism-related signature generated with the LASSO regression algorithm.

What role does NOTCH3 play in COAD based on the findings?

NOTCH3 is reported as overexpressed in COAD and is associated with promoting tumor growth, supported by multiple assays and functional experiments.

Sep 21, 2026

Uploaded by Levi