Ramachandran R, Bech P, Murphy K G, Caplin M E, Patel M, Vohra S, Khan M S, Dhillo W S, Sharma R, Palazzo F F, Win Z, Tan T, Khoo B, Meeran K, Frilling A, Ghatei M A, Bloom S R, Martin N M
European Neuroendocrine Tumor Society (ENETS) Centre of Excellence (R.R., P.B., K.G.M., M.P., S.V., W.S.D., R.S., F.F.P., Z.W., T.T., K.M., A.F., M.A.G., S.R.B., N.M.M.), Division of Diabetes, Endocrinology and Metabolism, Section of Investigative Medicine (R.R., P.B., K.G.M., M.P., S.V., W.S.D., T.T., K.M., M.A.G., S.R.B., N.M.M.), Imperial College London, London, W12 0HS United Kingdom; ENETS Centre of Excellence Neuroendocrine Tumor Unit (M.E.C., M.S.K., B.K.), Royal Free London NHS Foundation Trust Hospital, London, NW3 2QG. United Kingdom; Department of Gastroenterology (M.S.K.), University Hospital of Wales, Cardiff, CF14 4XW United Kingdom; Division of Experimental Medicine (R.S.), Departments of Surgery and Cancer (F.F.P.), and Radiology (Z.W.), Imperial College Healthcare NHS Trust, London, London W12 0HS, United Kingdom.
J Clin Endocrinol Metab. 2015 Apr;100(4):1520-8. doi: 10.1210/jc.2014-3640. Epub 2015 Feb 9.
Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker.
Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively.
MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes.
CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease.
CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.
神经内分泌肿瘤（NETs）患者的预后通常较差，这常常反映出诊断延迟。因此，需要准确且实用的NET标志物。可卡因和苯丙胺调节转录物（CART）肽是一种潜在的新型NET标志物。
使用放射免疫分析法（RIA）测定了353例NET（肾功能正常）患者和对照组中CART肽以及已确立的NET标志物嗜铬粒蛋白A（CgA）和嗜铬粒蛋白B（CgB）的循环水平。临床数据为回顾性收集。
在不同NET亚型中测定CART、CgA和CgB用于疾病诊断和评估疾病进展的比较及联合效用。
与单独使用每种生物标志物相比，CgA和CgB联合使用可提高肠道NET、非胃肠胰NET以及原发灶不明的NET患者的诊断准确性。检测CART并未进一步改善这些NET亚型的诊断。对于胰腺NET，CgB在检测疾病稳定方面优于CgA和CART（P < 0.007），而CgA和CART联合使用在识别疾病进展方面最有效。在嗜铬细胞瘤/副神经节瘤（PCC/PGL）中，CART是识别疾病稳定（P < 0.001）和疾病进展（P = 0.001）最有用的生物标志物。与此一致的是，PCC/PGL肿瘤切除后血浆CART降低，所有缓解患者中CART仍保持低水平，但疾病进展患者中CART升高。
CART是识别进展性胰腺NET的有用标志物。CART在检测稳定和进展性PCC/PGL方面优于CgA和CgB，可能作为PCC/PGL患者的监测标志物。
