研究动态
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鉴定用于预测结肠癌预后、免疫治疗功效和候选药物的氨基酸代谢重编程特征。

Identification of an Amino Acid Metabolism Reprogramming Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Colon Cancer.

发表日期:2024 Sep 02
作者: Fenqi Du, Xiangxin Wu, Yibo He, Shihui Zhao, Mingyu Xia, Bomiao Zhang, Jinxue Tong, Tianyi Xia
来源: GENES & DEVELOPMENT

摘要:

结肠癌在全球最常诊断的癌症中排名第三。氨基酸代谢重编程与结肠癌的发生、发展有关。我们从分子特征数据库中寻找与氨基酸代谢相关的氨基酸代谢基因(AMG)作为预后标志物,并构建了氨基酸代谢评分模型(AMS)。根据AMS将患者分为高AMS组和低AMS组,系统分析两组患者的预后特征、分子表型、体细胞突变特征、免疫细胞浸润特征以及免疫治疗效果。最后,还筛选了针对 AMG 的化合物。我们筛选出 6 个预后 AMG(P<0.05),并基于它们构建了 AMS 模型。 K-M曲线显示低AMS组的OS显着高于高AMS组(P < 0.05),这在多个数据集中得到了验证。不同AMS组具有不同的分子表型、体细胞突变特征和免疫细胞浸润特征。低AMS组免疫治疗效果较好。此外,我们预测了可以与 AMG 靶蛋白结合的潜在治疗化合物。 AMS模型可作为评价结肠癌预后、免疫浸润特征和免疫治疗反应能力的分层工具。基于 AMG 筛选出的化合物可能成为新型抗肿瘤药物。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下公司)的独家许可。
Colon cancer ranked third among the most frequently diagnosed cancers worldwide. Amino acid metabolic reprogramming was related to the occurrence and development of colon cancer. We looked for the amino acid metabolism genes (AMGs) associated with amino acid metabolism from molecular signatures database as prognostic markers and constructed amino acid metabolism scoring model (AMS). According to AMS, the patients were divided into high AMS and low AMS groups, and the prognostic characteristics, molecular phenotypes, somatic cell mutation characteristics, immune cell infiltration characteristics, and immunotherapy effect of the two groups were systematically analyzed. Finally, the compounds targeting AMGs were also screened. We screen out 6 prognostic AMGs (P < 0.05) and construct an AMS model based on them. K-M curve indicated that OS in low AMS group was significantly higher than that in high group (P < 0.05), which were validated in multiple datasets. And different AMS groups had different molecular phenotypes, somatic cell mutation characteristics and immune cell infiltration characteristics. Low AMS group had a better effect for immunotherapy. In addition, we predicted potential therapeutic compounds that could bind to AMGs target proteins. AMS model can be used as a hierarchical tool to evaluate the prognosis, immune infiltration characteristics and immunotherapy response ability of colon cancer. And the compounds screened based on AMGs may become new anti-tumor drugs.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.