Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China.
PeerJ. 2023 Feb 6;11:e14854. doi: 10.7717/peerj.14854. eCollection 2023.
Reprogramming of fatty acid metabolism is a newly-identified hallmark of malignancy. However, no studies have systematically investigated the fatty acid metabolism related-gene set in prostate cancer (PCa).
A cohort of 381 patients with gene expression and clinical data from The Cancer Genome Atlas was used as the training set, while another cohort of 90 patients with PCa from GEO (GSE70769) was used as the validation set. Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score. Associations between the risk score and clinical characteristics, immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) score, and response to chemotherapy were analyzed. Finally, the expression level of genes included in the model was validated using real-time PCR.
A prognostic risk model based on five fatty acid metabolism related genes (, , , , and ) were constructed. Tumors with higher risk score were associated with larger tumor size, lymph node involvement, higher Gleason score, and poorer biochemical recurrence (BCR)-free survival. Furthermore, the high- and low-risk tumors exhibited distinct immune cell infiltration features and immune-related pathway activation. High-risk tumors were associated with favorable response to immunotherapy as indicated by high TMB and low TIDE score, but poor response to bicalutamide and docetaxel chemotherapy.
This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.
脂肪酸代谢重编程是恶性肿瘤新的标志性特征之一。然而，目前尚无研究系统地研究前列腺癌（PCa）中与脂肪酸代谢相关的基因集。
使用来自癌症基因组图谱（TCGA）的 381 名患者的基因表达和临床数据作为训练集，而另一组来自 GEO（GSE70769）的 90 名 PCa 患者作为验证集。使用最小绝对收缩和选择算子（LASSO）-Cox 回归对差异表达的脂肪酸代谢相关基因进行分析，以建立脂肪酸代谢相关风险评分。分析风险评分与临床特征、免疫细胞浸润、肿瘤突变负担（TMB）、肿瘤免疫功能障碍和排除（TIDE）评分以及对化疗的反应之间的关系。最后，使用实时 PCR 验证模型中包含的基因的表达水平。
构建了一个基于五个脂肪酸代谢相关基因（，，，，和）的预后风险模型。风险评分较高的肿瘤与更大的肿瘤大小、淋巴结受累、更高的 Gleason 评分和较差的生化无复发生存（BCR）相关。此外，高风险和低风险肿瘤表现出不同的免疫细胞浸润特征和免疫相关途径激活。高风险肿瘤与较高的 TMB 和较低的 TIDE 评分相关，提示对免疫治疗有良好的反应，但对比卡鲁胺和多西他赛化疗的反应较差。
本研究建立了一个与 BCR 和对化疗和免疫治疗的反应相关的脂肪酸代谢相关基因特征，为 PCa 提供了一个新的治疗生物标志物。
