DataSheet6_Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression.zip

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.

背景：结直肠癌（COAD）与支链氨基酸（BCAA）代谢之间的相互作用尚未得到充分理解，这构成了一个亟待深入探究的关键领域。方法：本研究基于BCAA代谢，采用最小绝对收缩和选择算子（LASSO）回归算法构建了一个预后模型。通过qRT-PCR和Western blot分析技术，我们比较了COAD组织与邻近的非癌组织以及不同细胞系中NOTCH3的表达情况。此外，我们通过体外和体内实验研究了NOTCH3对COAD细胞增殖、侵袭和迁移的影响。结果：我们构建的与BCAA代谢相关的特征集（BRS）能够区分COAD患者之间的不同免疫特征、肿瘤突变负荷、免疫治疗反应以及药物敏感性。研究发现，NOTCH3在COAD中表达上调，并通过多种检测方法证实了其促进肿瘤生长的作用。该模型有效预测了COAD的预后和患者对治疗的反应，凸显了BCAA途径作为治疗靶点的潜力。结论：BRS在预测COAD的预后和治疗反应方面具有重要作用，NOTCH3在COAD的增殖、侵袭和迁移中扮演着显著角色。这些发现表明，针对BCAA代谢和NOTCH3有可能推进COAD的治疗策略。