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以指导治疗为目的评估膀胱癌中脂肪酸代谢情况。

Evaluation of aliphatic acid metabolism in bladder cancer with the goal of guiding therapeutic treatment.

作者信息

Song Tianbao, He Kaixiang, Ning Jinzhuo, Li Wei, Xu Tao, Yu Weimin, Rao Ting, Cheng Fan

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Oncol. 2022 Aug 18;12:930038. doi: 10.3389/fonc.2022.930038. eCollection 2022.

Abstract

Urothelial bladder cancer (BLCA) is a common internal malignancy with a poor prognosis. The re-programming of lipid metabolism is necessary for cancer cell growth, proliferation, angiogenesis and invasion. However, the role of aliphatic acid metabolism genes in bladder cancer patients has not been explored. The samples' gene expression and clinicopathological data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate, multivariate, and LASSO Cox regression were used to develop a BLCA prognostic model. GSVA was used to assess function, whereas pRRophetic was used to assess chemotherapeutic drug sensitivity. The twelve-gene signature may define the tumor immune milieu, according to the risk score model. We compared the expression of aliphatic acid metabolism genes in malignant and non-cancerous tissues and chose 90 with a false discovery rate of 0.05 for The Cancer Genome Atlas cohort. The prognostic risk score model can effectively predict BLCA OS. A nomogram including age, clinical T stage, gender, grade, pathological stage, and clinical M stage was developed as an independent BLCA prognostic predictor. The halfmaximal inhibitory concentration (IC50) was used to assess chemotherapeutic medication response. Sorafenib and Pyrimethamine were used to treat patients with low risk scores more sensitively than patients with high risk scores. Immunotherapy candidates with CMS1 exhibited higher risk ratings. The aliphatic acid prognostic risk score model can assess metabolic trends. Clinical stage and molecular subtype may be used to categorize individuals using the risk score.With this new paradigm, future cancer treatment and immunotherapy may be tailored to the patient's exact requirements.

摘要

尿路上皮膀胱癌(BLCA)是一种常见的内部恶性肿瘤,预后较差。脂质代谢重编程对于癌细胞的生长、增殖、血管生成和侵袭至关重要。然而,脂肪酸代谢基因在膀胱癌患者中的作用尚未得到探索。样本的基因表达和临床病理数据来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)。使用单变量、多变量和LASSO Cox回归来建立BLCA预后模型。基因集变异分析(GSVA)用于评估功能,而pRRophetic用于评估化疗药物敏感性。根据风险评分模型,这12个基因特征可能定义肿瘤免疫微环境。我们比较了恶性组织和非癌组织中脂肪酸代谢基因的表达,并为TCGA队列选择了90个错误发现率为0.05的基因。预后风险评分模型可以有效预测BLCA的总生存期(OS)。开发了一个包括年龄、临床T分期、性别、分级、病理分期和临床M分期的列线图,作为独立的BLCA预后预测指标。半数最大抑制浓度(IC50)用于评估化疗药物反应。索拉非尼和乙胺嘧啶用于治疗低风险评分患者比高风险评分患者更敏感。具有CMS1的免疫治疗候选者表现出更高的风险评级。脂肪酸预后风险评分模型可以评估代谢趋势。临床分期和分子亚型可用于根据风险评分对个体进行分类。有了这个新范式,未来的癌症治疗和免疫治疗可能会根据患者的确切需求进行定制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e635/9433665/9997ea2663cd/fonc-12-930038-g001.jpg

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