Ma Zhaofeng, Zheng Man, Liu Pulin
Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong Province, 257091, China.
Hereditas. 2025 Apr 7;162(1):55. doi: 10.1186/s41065-025-00425-4.
Breast cancer (BRCA) is a malignancy originating in the breast cells, characterized by a poor overall survival rate. Post-resection, chemotherapy is commonly recommended as a primary therapeutic approach; however, its efficacy remains limited. Recent advancements in lipidomics and metabolomics have provided new insights into the intricate landscape of fatty acid metabolism (FAM) and the fatty acid lipidome in both health and disease. A growing body of evidence suggests that dysregulations in FAM and fatty acid levels play a significant role in cancer initiation and progression. Despite these advances, the precise mechanisms through which FAM mediates the anti-cancer effects of lobaplatin in BRCA remain poorly understood and warrant further investigation.
GEO and TCGA data were classified into two types. We aimed to show how FAMGs influence immune function, immune checkpoints, and m6a in BRCA. A co-expression analysis discovered that gene expression is strongly connected to pyroptosis. The TCGA gathered information about mRNAsi, gene mutations, CNV, and clinical features.
In the low-risk group, overall survival (OS) is longer. GSEA was utilized to identify immune and tumor-related pathways. Most of the FAMG-derived prognostic signatures predominantly modulate immunological and oncogenic signaling pathways, including the Wnt, neurotrophin, chemokine, and calcium signaling cascades. Among the genes involved are CEL, WT1, and ULBP2. Expression levels varied as well. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all pointed to the gene.
The primary objective of this study is to identify and validate BRCA-associated FAMGs that can serve as prognostic indicators and provide insights into immune system function, while also offering evidence to support the development of fatty acid metabolism-related molecularly targeted therapeutics. Consequently, FAMGs and their interactions with the immune system, as well as their role in BRCA, may emerge as promising therapeutic targets.
乳腺癌(BRCA)是一种起源于乳腺细胞的恶性肿瘤,总体生存率较低。切除术后,化疗通常被推荐作为主要治疗方法;然而,其疗效仍然有限。脂质组学和代谢组学的最新进展为健康和疾病状态下脂肪酸代谢(FAM)及脂肪酸脂质组的复杂情况提供了新的见解。越来越多的证据表明,FAM和脂肪酸水平的失调在癌症的发生和发展中起重要作用。尽管有这些进展,但FAM介导洛铂对BRCA抗癌作用的确切机制仍知之甚少,值得进一步研究。
将GEO和TCGA数据分为两种类型。我们旨在展示FAMG如何影响BRCA中的免疫功能、免疫检查点和m6A。共表达分析发现基因表达与细胞焦亡密切相关。TCGA收集了有关mRNAsi、基因突变、拷贝数变异(CNV)和临床特征的信息。
在低风险组中,总生存期(OS)更长。利用基因集富集分析(GSEA)来识别免疫和肿瘤相关途径。大多数FAMG衍生的预后特征主要调节免疫和致癌信号通路,包括Wnt、神经营养因子、趋化因子和钙信号级联。涉及的基因包括CEL、WT1和ULBP2。表达水平也有所不同。预后模型、CNV、单核苷酸多态性(SNP)和药物敏感性均指向该基因。
本研究的主要目的是识别和验证与BRCA相关的FAMG,其可作为预后指标并深入了解免疫系统功能,同时也为支持脂肪酸代谢相关分子靶向治疗的开发提供证据。因此,FAMG及其与免疫系统的相互作用,以及它们在BRCA中的作用,可能成为有前景的治疗靶点。