Jiménez-Franco Andrea, Jiménez-Aguilar Juan Manuel, Canela-Capdevila Marta, García-Pablo Raquel, Castañé Helena, Martínez-Navidad Cristian, Araguas Pablo, Malavé Bárbara, Benavides-Villarreal Rocío, Acosta Johana C, Onoiu Alina Iuliana, Somaiah Navita, Camps Jordi, Joven Jorge, Arenas Meritxell
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan de Reus, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Av. Dr. Josep Laporte 2, 43204 Reus, Spain.
Department of Radiation Oncology, Hospital Universitari Sant Joan de Reus, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Av. Dr. Josep Laporte 2, 43204 Reus, Spain.
Biomedicines. 2024 Sep 26;12(10):2196. doi: 10.3390/biomedicines12102196.
: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. : We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. : Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. : Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.
早期乳腺癌（BC）的治疗包括手术，随后进行辅助放疗、化疗、激素治疗或免疫治疗。然而，这些干预措施对代谢重编程的影响尚不清楚。本研究探讨了不同治疗后BC患者血浆代谢组的变化，以加深我们对BC病理生理学、预后的理解，并确定潜在的生物标志物。
我们纳入了52名被诊断为BC且拟接受手术作为主要肿瘤治疗的女性。在诊断时、术后两周和放疗后一个月采集血样。49名健康女性的血浆样本作为对照。靶向代谢组学评估了74种代谢物，涵盖碳水化合物、氨基酸、脂质、核苷酸途径、能量代谢和外源性生物降解。
治疗前，BC患者在碳水化合物、核苷酸、脂质和氨基酸代谢方面表现出显著变化。我们注意到在不同治疗过程中特定代谢物水平（次黄嘌呤、3-磷酸甘油酸、木糖酸和麦芽糖）逐渐恢复，表明核苷酸和碳水化合物代谢途径正常化。此外，我们观察到十二烷酸浓度增加，这是一种与癌症保护相关的代谢物。这些差异以高特异性和敏感性区分了患者与对照。
我们的初步研究表明，肿瘤治疗使患者的代谢朝着有利的方向改变，有利于细胞增殖的途径减少，抗癌分子水平增加。这些发现强调了代谢组学在识别每种癌症治疗影响的生物途径及其产生的代谢后果方面的关键作用。此外，它有助于识别疾病发生和进展的潜在生物标志物。
