Mariën Laura, Islam Odeta, Chhajlani Siddharth, Lybaert Willem, Peeters Marc, Van Camp Guy, Op de Beeck Ken, Vandamme Timon
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650, Edegem, Belgium.
Integrated Personalized and Precision Oncology Network (IPPON), Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Curr Treat Options Oncol. 2023 Dec;24(12):1833-1851. doi: 10.1007/s11864-023-01147-3. Epub 2023 Nov 22.
Given the considerable heterogeneity in neuroendocrine neoplasms (NENs), it appears unlikely that a sole biomarker exists capable of fully capturing all useful clinical aspects of these tumors. This is reflected in the abundant number of biomarkers presently available for the diagnosis, prognosis, and monitoring of NEN patients. Although assessment of immunohistochemical and radiological markers remains paramount and often obligatory, there has been a notable surge of interest in circulating biomarkers over the years given the numerous benefits associated with liquid biopsies. Currently, the clinic primarily relies on single-analyte assays such as the chromogranin A assay, but these are far from ideal because of limitations such as compromised sensitivity and specificity as well as a lack of standardization. Consequently, the quest for NEN biomarkers continued with the exploration of multianalyte markers, exemplified by the development of the NETest and ctDNA-based analysis. Here, an extensive panel of markers is simultaneously evaluated to identify distinct signatures that could enhance the accuracy of patient diagnosis, prognosis determination, and response to therapy prediction and monitoring. Given the promising results, the development and implementation of these multianalyte markers are expected to usher in a new era of NEN biomarkers in the clinic. In this review, we will outline both clinically implemented and more experimental circulating markers to provide an update on developments in this rapidly evolving field.
鉴于神经内分泌肿瘤（NENs）存在相当大的异质性，似乎不太可能存在一种单一的生物标志物能够完全涵盖这些肿瘤所有有用的临床特征。这反映在目前可用于NEN患者诊断、预后和监测的大量生物标志物上。尽管免疫组化和放射学标志物的评估仍然至关重要且常常是必需的，但鉴于液体活检有诸多益处，近年来对循环生物标志物的兴趣显著增加。目前，临床主要依赖单一分析物检测，如嗜铬粒蛋白A检测，但由于敏感性和特异性受损以及缺乏标准化等局限性，这些检测远非理想。因此，对NEN生物标志物的探索继续进行，对多分析物标志物进行了探索，以NETest和基于ctDNA的分析为代表。在此，同时评估大量标志物以识别不同的特征，从而提高患者诊断、预后判断以及治疗反应预测和监测的准确性。鉴于取得了有前景的结果，这些多分析物标志物的开发和应用有望在临床上开创NEN生物标志物的新时代。在本综述中，我们将概述已在临床应用的和更多实验性的循环标志物，以提供这一快速发展领域的最新进展情况。
