SDC2和FN作为肥胖伴淋巴结转移乳腺癌患者循环细胞外囊泡中的货物蛋白。

SDC2 and FN as cargo proteins in circulating extracellular vesicles in obese breast cancer patients with lymph node metastasis.

作者信息

Talat Liali Yousef, Mohamed Ghada, Ibraheem Maher H, WalyEldeen Amr Ahmed, Hassan Hebatallah, Ibrahim Sherif Abdelaziz

机构信息

Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt.

Department of Pathology, National Cancer Institute, Cairo University, Cairo, 11796, Egypt.

出版信息

Sci Rep. 2025 Sep 12;15(1):32498. doi: 10.1038/s41598-025-17638-2.

DOI:10.1038/s41598-025-17638-2

PMID:40940401

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12432118/

Abstract

Lymph node metastasis (LNM) is a pivotal determinant of breast cancer (BC) patient prognosis and treatment efficacy. Cell surface heparan sulfate proteoglycans (HSPGs), namely, syndecan-1 (SDC1), SDC2, and SDC4, are involved in cancer progression, metastasis, and regulate extracellular vesicles (EVs) biogenesis, including the microvesicles (MVs). This study analyzed MV-enriched EVs isolated from blood plasma of BC patients with negative (n = 19) and positive (n = 20) LNM (nLNM and pLNM, respectively) using differential centrifugation. Western blot analysis revealed significantly elevated SDC2 levels in MV-enriched EVs from pLNM cases compared to nLNM. Additionally, fibronectin (FN), a SDC2-interacting protein identified through STRING analysis, was also upregulated in pLNM MV-enriched EVs. In contrast, qRT-PCR showed reduced SDC2 (P < 0.01) and FN (P < 0.05) mRNA levels in tumor tissues of pLNM patients compared to nLNM. ROC analysis highlighted the diagnostic value of SDC2 (AUC: 0.8376) and FN (AUC: 0.8803) mRNA in differentiating LNM status. Bioinformatics analyses further confirmed the association of SDC2 and FN expression with BC staging and prognosis. These findings underscore the potential of circulating MV-enriched EV-associated SDC2 and FN, along with their tumor tissue mRNA expression, as potential predictive biomarkers for LNM and chemotherapy response in chemotherapy-naïve obese BC patients.

摘要

淋巴结转移（LNM）是乳腺癌（BC）患者预后和治疗效果的关键决定因素。细胞表面硫酸乙酰肝素蛋白聚糖（HSPGs），即 syndecan-1（SDC1）、SDC2 和 SDC4，参与癌症进展、转移，并调节细胞外囊泡（EVs）的生物发生，包括微囊泡（MVs）。本研究使用差速离心法分析了从淋巴结转移阴性（n = 19）和阳性（n = 20）的 BC 患者血浆中分离出的富含 MV 的 EVs（分别为 nLNM 和 pLNM）。蛋白质印迹分析显示，与 nLNM 相比，pLNM 病例中富含 MV 的 EVs 中 SDC2 水平显著升高。此外，通过 STRING 分析鉴定出的与 SDC2 相互作用的蛋白纤连蛋白（FN）在富含 pLNM MV 的 EVs 中也上调。相反，qRT-PCR 显示，与 nLNM 相比，pLNM 患者肿瘤组织中 SDC2（P < 0.01）和 FN（P < 0.05）的 mRNA 水平降低。ROC 分析突出了 SDC2（AUC：0.8376）和 FN（AUC：0.8803）mRNA 在区分 LNM 状态方面的诊断价值。生物信息学分析进一步证实了 SDC2 和 FN 表达与 BC 分期和预后的关联。这些发现强调了循环中富含 MV 的 EV 相关的 SDC2 和 FN 及其肿瘤组织 mRNA 表达作为未接受过化疗的肥胖 BC 患者 LNM 和化疗反应潜在预测生物标志物的潜力。