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，这构成了一个亟待研究的关键领域。方法：我们基于BCAA代谢利用最小绝对收缩和选择算子（LASSO）回归算法开发了一个预后模型。我们采用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹分析来检测结直肠癌组织与相邻的非癌组织以及各种细胞系中NOTCH3的表达。我们还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：我们的BCAA代谢相关特征（BRS）能够区分COAD患者之间的不同免疫特征、肿瘤突变负荷、对免疫治疗的反应以及药物敏感性。研究发现NOTCH3在COAD中过表达，并通过多种实验验证其促进肿瘤生长的作用。该模型有效地预测了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的预后和治疗反应中发挥着重要作用，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可能推动COAD治疗策略的进步。