Tamarindo G H, Novais A A, Frigieri B M, Alves D L, de Souza C A, Amadeu A, da Silveira J C, Souza F F, Bordin N A, Chuffa L G A, Zuccari D A P C
Molecular Investigation of Cancer Laboratory (MICL), Department of Molecular Biology, Faculdade de Medicina de São José do Rio Preto/(FAMERP), São José do Rio Preto, SP, 15090-000, Brazil.
Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, 13083-100, Brazil.
Sci Rep. 2025 Apr 9;15(1):12122. doi: 10.1038/s41598-025-95232-2.
Extracellular vesicles (EVs) derived from plasma, measuring up to 150 nm, act as molecular messengers transmitting critical information to recipient cells, making them valuable candidates for liquid biopsy applications in cancer diagnostics. Triple-negative breast cancer (TNBC) is particularly challenging due to its aggressive nature, metastasis potential, and limited treatment options. This study aimed to identify EV-associated proteins in blood samples that could serve as potential TNBC biomarkers. Using mass spectrometry-based proteomic analysis, we detected unique and differentially expressed proteins across healthy individuals, patients with benign breast conditions, and those with TNBC. While EVs size and concentration showed no differences, the proteomic profile varied significantly among these groups. Several immune-related proteins were found exclusively in healthy individuals but were diminished in both benign and malignant cases. We also assessed the impact of surgery on EVs protein content and identified Histone H2A as a TNBC-specific marker present before surgery. Its expression was further validated through immunohistochemistry and Western blotting in TNBC biopsies and cell lines. Notably, surgical intervention enhanced immune response pathways in TNBC patients. In conclusion, liquid biopsy has the potential to serve as a non-invasive tool for TNBC diagnosis and monitoring, revealing a post-surgery molecular landscape that supports combining immunotherapy with mastectomy.
源自血浆的细胞外囊泡（EVs）直径可达150纳米，作为分子信使向受体细胞传递关键信息，使其成为癌症诊断中液体活检应用的有价值候选物。三阴性乳腺癌（TNBC）因其侵袭性、转移潜力和有限的治疗选择而极具挑战性。本研究旨在鉴定血液样本中可作为潜在TNBC生物标志物的EV相关蛋白。通过基于质谱的蛋白质组学分析，我们在健康个体、患有良性乳腺疾病的患者以及TNBC患者中检测到了独特且差异表达的蛋白质。虽然EVs的大小和浓度没有差异，但这些组之间的蛋白质组学特征有显著差异。几种免疫相关蛋白仅在健康个体中发现，但在良性和恶性病例中均减少。我们还评估了手术对EVs蛋白质含量的影响，并确定组蛋白H2A为术前存在的TNBC特异性标志物。通过免疫组织化学和蛋白质印迹法在TNBC活检组织和细胞系中进一步验证了其表达。值得注意的是，手术干预增强了TNBC患者的免疫反应途径。总之，液体活检有潜力作为TNBC诊断和监测的非侵入性工具，揭示术后分子格局，支持将免疫疗法与乳房切除术相结合。
