利用 MALDI-MSI 确定前列腺癌组织芯片新结果队列中的 N-糖和胶原蛋白/细胞外基质蛋白组成

IF 2 Q3 ONCOLOGY Cancer research communications Pub Date : 2024-09-30 DOI:10.1158/2767-9764.CRC-24-0152
Jordan P Hartig, Kaitlyn Bejar, Lyndsay E A Young, Grace Grimsley, Jennifer R Bethard, Dean A Troyer, Javier Hernandez, Jennifer D Wu, Joseph E Ippolito, Lauren E Ball, Jonathan A L Gelfond, Teresa L Johnson-Pais, Anand S Mehta, Robin J Leach, Peggi M Angel, Richard R Drake
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引用次数: 0

摘要

前列腺癌是一个重大的健康问题,其转移带来了重大的临床挑战,并导致患者预后不佳。尽管筛查和治疗取得了进展,但在前列腺切除术时预测前列腺癌进展的新型生物标记物的需求仍然十分迫切。在这里,我们评估了异常 N-糖基化模式和细胞外基质蛋白的改变,将其作为预测前列腺癌严重程度的潜在生物标志物。组织微阵列切片来自原发性前列腺切除术标本,这些标本根据 >5 年的疾病进展结果分为 "无疾病证据 (NED)" 和 "转移 (MET) "两类。通过序列质谱成像技术分析了福尔马林固定石蜡包埋核心中的 N-聚糖和细胞外基质(ECM)成分。结果发现,与 NED 组织相比,MET 组织中的双链和多链核岩藻糖基化 N-聚糖明显上调。在 NED 和 MET 组群中均观察到 ECM 成分的改变,尤其是胶原种类和羟脯氨酸含量的改变。结果表明,前列腺癌组织中 ECM 蛋白质和糖基化含量的协调变化可预测前列腺切除术后的疾病进展。
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Determining the N-Glycan and Collagen/Extracellular Matrix Protein Compositions in a Novel Outcome Cohort of Prostate Cancer Tissue Microarrays Using MALDI-MSI.

Prostate cancer is a significant health concern, with metastasis posing major clinical challenges and resulting in poor patient outcome. Despite screening and treatment advances, a critical need for novel biomarkers to predict prostate cancer progression at the time of prostatectomy persists. Here, we assessed aberrant N-glycosylation patterns and alterations in extracellular matrix proteins as potential biomarkers of predicting prostate cancer severity in a unique patient outcome cohort. Tissue microarray slides were assembled from primary prostatectomy specimens that were categorized into "no evidence of disease (NED)" and "metastasis (MET)" designations based on >5-year disease progression outcomes. Serial mass spectrometry imaging techniques were performed to analyze N-glycans and extracellular matrix (ECM) components in formalin-fixed paraffin-embedded cores. The results revealed a significant upregulation of bisecting and multi-antennary core fucosylated N-glycans in MET tissues when compared to NED tissues. Alterations in ECM composition in both NED and MET cohorts were observed, particularly in collagen species and the amount of hydroxyproline content. Results suggest a coordinated alteration of ECM protein and glycosylation content in prostate cancer tissues can be predictive for post-prostatectomy disease progression.

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