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寻找神经内分泌肿瘤的新型生物标志物:神经内分泌肿瘤患者中嗜铬粒蛋白 A 与炎症细胞因子的对比分析。

Searching for New Biomarkers of Neuroendocrine Tumors: A Comparative Analysis of Chromogranin A and Inflammatory Cytokines in Patients with Neuroendocrine Tumors.

机构信息

Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland.

Department of Psychiatry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland.

出版信息

Curr Oncol. 2024 Oct 12;31(10):6110-6132. doi: 10.3390/curroncol31100456.

Abstract

Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of 84 NEN patients and 40 healthy controls using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA. Significant alterations in cytokine levels were observed in the NEN patients compared to the controls, including elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), and reduced levels of angiogenic factors like platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor beta (TNF-β). Notably, cytokines such as growth-regulated alpha protein (GRO-α) and TNF-β demonstrated strong potential as diagnostic markers, with receiver operating characteristic (ROC) curve analyses showing high sensitivity and specificity. Additionally, a positive correlation was found between CgA levels and several inflammatory cytokines, suggesting their synergistic role in tumor progression. These findings highlight the limited reliability of CgA alone as a diagnostic marker and underscore the importance of a multi-marker approach in diagnosing and monitoring NENs. Further research on a larger cohort is necessary to validate these biomarkers and their potential clinical applications.

摘要

神经内分泌肿瘤(NENs)因其异质性和非特异性临床表现而具有诊断挑战性。本研究旨在探索 NENs 的新型生物标志物。采用酶联免疫吸附试验(ELISA)和多重 ELISA 分析了 84 名 NEN 患者和 40 名健康对照者的血清嗜铬粒蛋白 A(CgA)水平和 48 种炎症细胞因子。与对照组相比,NEN 患者的细胞因子水平存在显著改变,包括促炎细胞因子(如白细胞介素(IL)-6、IL-8 和肿瘤坏死因子 alpha(TNF-α))水平升高,以及血管生成因子(如血小板衍生生长因子-BB(PDGF-BB)和肿瘤坏死因子 beta(TNF-β))水平降低。值得注意的是,细胞因子如生长调节素 alpha 蛋白(GRO-α)和 TNF-β 具有作为诊断标志物的强大潜力,受试者工作特征(ROC)曲线分析显示出高灵敏度和特异性。此外,CgA 水平与几种炎症细胞因子之间存在正相关,表明它们在肿瘤进展中具有协同作用。这些发现强调了 CgA 作为单一诊断标志物的可靠性有限,并强调了采用多标志物方法诊断和监测 NENs 的重要性。需要对更大的队列进行进一步研究,以验证这些生物标志物及其潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b923/11506232/417f2ddcc289/curroncol-31-00456-g005.jpg

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