A novel fatty acid metabolism-related gene signature predicts the prognosis, tumor immune properties, and immunotherapy response of colon adenocarcinoma patients.
A novel fatty acid metabolism-related gene signature predicts the prognosis, tumor immune properties, and immunotherapy response of colon adenocarcinoma patients.
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一种新的脂肪酸代谢相关基因特征可预测结肠腺癌患者的预后、肿瘤免疫特性和免疫治疗反应。
DOI：
10.1096/fba.2022-00017
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发表时间：
2022-09
影响因子：
2.7
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中科院分区：
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结肠腺癌（COAD）是一种发病率高、死亡率高的疾病。尽管脂肪酸代谢的变化在代谢物谱中最大程度地促进了肿瘤的生长和转移，但脂肪酸代谢相关基因（FAMRGs）在COAD中的作用尚未得到深入的研究。在这里，临床数据以及基因表达谱是从癌症基因组图谱（TCGA）数据库中提取的。基于FAMRG表达数据和临床信息，使用LASSO以及多因素和单因素Cox回归分析建立FAMRG风险特征。然后，使用nomogram建立自定义的预后预测模型，并使用校准曲线和接收者工作特征曲线来评估nomogram的预测性能和判别能力。最后，我们进行了一些研究来评估独立的FAMRGs对COAD的影响，包括无监督聚类分析、功能分析和药物敏感性分析。本研究纳入了367例患者，基于对FAMRG表达数据和临床信息的详细检查，在培训队列中发现了12‐FAMRG风险特征。之后，计算风险评分将患者分为低风险组和高风险组，Kaplan-Meier曲线分析显示，低风险组患者的总生存率（OS）较高。多变量Cox回归分析显示FAMRG与预后显著相关，并使用验证数据集进行验证。然后，利用临床变量和风险特征，我们开发并验证了OS的预测图。功能表征表明这一特征与免疫细胞浸润和免疫调节有很强的相关性。此外，通过评估GDSC数据库，确定高危组对许多化疗药物和靶向药物表现出耐药性，包括VX.680、吉西他滨、阿霉素和紫杉醇。总之，我们已经揭示了FAMRG风险特征在预测COAD患者预后和免疫治疗反应方面的重要性，我们的发现可能有助于增强对代谢途径的理解和未来创新COAD治疗方法的开发。
Colon adenocarcinoma (COAD) has a high incidence and death rate. Despite the fact that change in fatty acid metabolism promotes tumor growth and metastasis to the greatest degree among metabolite profiles, a thorough investigation on the involvement of fatty acid metabolism‐related genes (FAMRGs) in COAD has yet not been conducted. Here, the clinical data as well as the gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) database. Based on the FAMRG expression data and clinical information, a FAMRG risk signature was developed using LASSO as well as multivariate and univariate Cox regression analyses. Then, the nomogram was used to create a customized prognostic prediction model, and the calibration and receiver operating characteristic curves were used to evaluate the nomogram's prediction performance and discriminative capability. Lastly, a number of studies were conducted to assess the influence of independent FAMRGs on COAD, including unsupervised cluster analysis, functional analysis, and drug sensitivity analysis. Three hundred and sixty‐seven patients were included in this study, and a 12‐FAMRG risk signature was discovered in the training cohort based on a detailed examination of the FAMRGs expression data and clinical information. After that, risk scores were computed to classify patients into low or high‐risk groups, and the Kaplan–Meier curve analysis revealed that patients in the low‐risk group exhibited an elevated overall survival (OS) rate. The FAMRG was shown to be substantially correlated with prognosis in multivariate Cox regression analysis and was validated using the validation dataset. Then, using the clinical variables and risk signature, we developed and validated a prediction nomogram for OS. Functional characterization showed a strong correlation between this signature and immune cell infiltration and immune modulation. Additionally, by evaluating the GDSC database, it was determined that the high‐risk group exhibited medication resistance to many chemotherapeutic and targeted medicines, including VX.680, gemcitabine, doxorubicin, and paclitaxel. Overall, we have revealed the significance of a FAMRG risk signature for predicting the prognosis and response to immunotherapy in COAD, and our findings might contribute to an enhanced comprehension of metabolic pathways and the future development of innovative COAD therapeutic methods.