血浆 NRP2 和 VEGF-C 水平与前列腺癌疾病严重程度的关联。
Association of plasma NRP2 and VEGF-C levels with prostate cancer disease severity.
发表日期:2023 Nov 09
作者:
Sarah A Mullen, Dipanwita Das, Negin Ziamiavaghi, Robin High, Kaustubh Datta, Benjamin A Teply
来源:
MOLECULAR & CELLULAR PROTEOMICS
摘要:
组织中的 Neuropilin 2 (NRP2) 表达是侵袭性前列腺癌的独立预后因素。由于 NRP2 通路激活被认为部分是通过继发性耐药发生的,因此诊断时收集的初始组织活检标本中 NRP2 的量化在识别发病和死亡风险最高的患者方面可能作用有限。鉴于转移组织只是偶尔获得用于分析,因此需要开发指示 NRP2 通路激活的血浆生物标志物,以潜在地告知前列腺癌预后。因此,我们研究了 NRP2 或血管内皮生长因子 C (VEGF-C)(一种已知的 NRP2 可溶性配体)的血浆水平是否可以预测前列腺癌。我们假设血浆 NRP2 和 VEGF-C 与更晚期的疾病或复发性疾病有关。通过酶联免疫分析对取自机会性生物库中 145 名前列腺癌患者的血浆样本中的 NRP2 和 VEGF-C 水平进行定量。这些患者要么(1)新诊断(N = 28),(2)缓解期(N = 56),或(3)疾病复发(N = 61)。来自 15 名没有已知恶性肿瘤的成年男性的血浆样本作为比较队列。进行统计分析以调查血浆 NRP2/VEGF-C 与患者结果的关系,调整年龄、种族、前列腺特异性抗原 (PSA)、格里森评分和诊断时的肿瘤分期。NRP2 和 VEGF-C 水平均未受到影响。与非癌症对照相比,癌症患者存在显着差异。我们观察到血浆 NRP2 与疾病严重程度之间没有明确的关联。血浆 VEGF-C 增加与疾病缓解显着相关,并与 I/II 期和中危格里森评分相关。 NRP2 和 VEGF-C 均与 PSA 水平无关。尽管组织 NRP2 表达与严重疾病相关,但血浆 NRP2 并未观察到这一点。血浆 NRP2 水平与疾病严重程度或复发无关。 VEGF-C 在缓解期和病情较轻的患者中最高。需要进一步的研究来确定评估肿瘤 NRP2 状态的非侵入性方法。© 2023 作者。 《前列腺》由 Wiley periodicals LLC 出版。
Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue biopsy specimens collected at diagnosis may have limited utility in identifying patients at highest risk for morbidity and mortality. Given that metastatic tissue is only occasionally obtained for analysis, there is a need for development of a plasma biomarker indicative of NRP2 pathway activation to potentially inform prostate cancer prognosis. Therefore, we investigated if plasma levels of NRP2 or vascular endothelial growth factor C (VEGF-C), a known soluble ligand of NRP2, are prognostic for prostate cancer. We hypothesized that plasma NRP2 and VEGF-C would be associated with more advanced disease or relapsed disease.NRP2 and VEGF-C levels were quantified by enzyme-linked immunoassay in plasma samples obtained from 145 prostate cancer patients in an opportunistic biobank. These patients were either (1) newly diagnosed (N = 28), (2) in remission (N = 56), or (3) relapsed disease (N = 61). Plasma samples from 15 adult males without known malignancy served as a comparator cohort. Statistical analysis was performed to investigate the association of plasma NRP2/VEGF-C with patient outcomes, adjusting for age, race, prostate-specific antigen (PSA), Gleason score, and tumor stage at diagnosis.Neither NRP2 nor VEGF-C levels were significantly different in cancer patients compared to noncancer controls. We observed no clear association between plasma NRP2 and disease severity. Increased plasma VEGF-C was significantly associated with disease remission and correlated with Stage I/II and intermediate-risk Gleason score. Neither NRP2 nor VEGF-C correlated with PSA level.Although tissue NRP2 expression correlates with severe disease, this was not observed for plasma NRP2. Plasma NRP2 levels did not correlate with disease severity or relapse. VEGF-C was highest in patients in remission and with less severe disease. Future investigation is needed to identify noninvasive methods to assess tumor NRP2 status.© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.