Danielle A Scott, Souvik Seal, Laura Spruill, Jaclyn Dunne, Graham Colditz, Anand S Mehta, Richard R Drake, Marvella E Ford, Peggi M Angel
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引用次数: 0
摘要
三阴性乳腺癌(TNBC)是一种缺乏靶向治疗的侵袭性乳腺癌亚型。虽然异常n -糖基化是恶性肿瘤的标志,但核心聚焦(CF)和外臂聚焦(OAF) n -聚糖在TNBC进展和患者生存中的具体作用仍未得到充分探讨。本研究利用基质辅助激光解吸电离成像质谱(MALDI IMS)的多重糖组学技术,对59例TNBC肿瘤的348种n -聚糖进行了空间分析,这些肿瘤的临床特征包括生存数据。空间分析显示CF和OAF异构体在肿瘤微环境中的定位模式不同。引人注目的是,OAF聚糖(而非CF)与肿瘤分期密切相关,从I期到III期表达增加,然后在IV期下降。此外,68种n -聚糖与生存结果显著相关;其中36个(52%)是经oaf修饰的,包括先前与乳腺癌转移有关的聚乳胺结构。OAF多乳糖胺的高表达与预后不良相关,并且在早期TNBC肿瘤中可检测到,强调了它们作为预后生物标志物的潜力。意义:这些发现表明,OAF n -聚糖是动态的、结构特异性的TNBC进展和生存标志物,其早期检测和强大的预后价值突出了患者分层和个性化治疗的潜在效用。
Fucosylated N-Glycan Landscape of Triple Negative Breast Cancer.
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapies. While aberrant N-glycosylation is a hallmark of malignancy, the specific roles of core fucosylated (CF) and outer arm fucosylated (OAF) N-glycans in TNBC progression and patient survival remains underexplored. This study utilized multiplexed glycomics by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to spatially profile 348 N-glycans in 59 TNBC tumors with clinical characteristics including survival data. Spatial analysis revealed distinct localization patterns of CF and OAF isomers within tumor microenvironments. Strikingly, OAF glycans, but not CF, were strongly associated with tumor stage, with expression increasing from Stage I to III, then declining in Stage IV. Furthermore, 68 N-glycans were significantly associated with survival outcomes; 36 (52%) of these were OAF-modified, including polylactosamine structures previously linked to metastasis in breast cancer. High expression of OAF polylactosamines correlated with poor prognosis and were detectable in early-stage TNBC tumors, underscoring their potential as prognostic biomarkers. Implications: These findings demonstrate that OAF N-glycans are dynamic, structure-specific markers of TNBC progression and survival and their early detection and strong prognostic value highlight potential utility in patient stratification and personalized therapy.
期刊介绍:
Molecular Cancer Research publishes articles describing novel basic cancer research discoveries of broad interest to the field. Studies must be of demonstrated significance, and the journal prioritizes analyses performed at the molecular and cellular level that reveal novel mechanistic insight into pathways and processes linked to cancer risk, development, and/or progression. Areas of emphasis include all cancer-associated pathways (including cell-cycle regulation; cell death; chromatin regulation; DNA damage and repair; gene and RNA regulation; genomics; oncogenes and tumor suppressors; signal transduction; and tumor microenvironment), in addition to studies describing new molecular mechanisms and interactions that support cancer phenotypes. For full consideration, primary research submissions must provide significant novel insight into existing pathway functions or address new hypotheses associated with cancer-relevant biologic questions.