Levy Sonja, Kilgallen Aoife B, Korse Catharina M, Oerlemans Marish I F J, Sluijter Joost P G, van Laake Linda W, Valk Gerlof D, Tesselaar Margot E T
Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Regenerative Medicine Centre Utrecht, Circulatory Health Laboratory, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
Cancers (Basel). 2022 May 10;14(10):2361. doi: 10.3390/cancers14102361.
Carcinoid heart disease (CHD) is a rare fibrotic cardiac complication of neuroendocrine tumors. Besides known biomarkers N-Terminal pro-B-type natriuretic peptide (NT-proBNP) and serotonin, activin A, connective tissue growth factor (CTGF), and soluble suppression of tumorigenicity 2 (sST2) have been suggested as potential biomarkers for CHD. Here, we validated the predictive/diagnostic value of these biomarkers in a case-control study of 114 patients between 1990 and 2021. Two time-points were analyzed: T0: liver metastasis without CHD for all patients. T1: confirmed CHD in cases (CHD+, n = 57); confirmed absence of CHD five or more years after liver metastasis in controls (CHD−, n = 57). Thirty-one (54%) and 25 (44%) females were included in CHD+ and CHD− patients, respectively. Median age was 57.9 years for CHD+ and 59.7 for CHD- patients (p = 0.290). At T0: activin A was similar across both groups (p = 0.724); NT-proBNP was higher in CHD+ patients (17 vs. 6 pmol/L, p = 0.016), area under the curve (AUC) 0.84, and the most optimal cut-off at 6.5 pmol/L. At T1: activin A was higher in CHD+ patients (0.65 vs. 0.38 ng/mL, p = 0.045), AUC 0.62, without an optimal cut-off value. NT-pro-BNP was higher in CHD+ patients (63 vs. 11 pmol/L, p < 0.001), AUC 0.89, with an optimal cut-off of 27 pmol/L. Serotonin (p = 0.345), sST2 (p = 0.867) and CTGF (p = 0.232) levels were similar across groups. This large validation study identified NT-proBNP as the superior biomarker for CHD. Patients with elevated serotonin levels and NT-proBNP levels between 6.5 and 27 pmol/L, and specifically >27 pmol/L, should be monitored closely for the development of CHD.
类癌性心脏病（CHD）是神经内分泌肿瘤罕见的纤维化心脏并发症。除了已知的生物标志物N端前脑钠肽（NT-proBNP）和血清素外，激活素A、结缔组织生长因子（CTGF）和可溶性肿瘤抑制因子2（sST2）也被认为是CHD的潜在生物标志物。在此，我们在一项针对1990年至2021年间114例患者的病例对照研究中验证了这些生物标志物的预测/诊断价值。分析了两个时间点：T0：所有患者无CHD的肝转移。T1：病例组确诊为CHD（CHD+，n = 57）；对照组肝转移后五年或更长时间确诊无CHD（CHD−，n = 57）。CHD+组和CHD−组分别纳入了31名（54%）和25名（44%）女性。CHD+组的中位年龄为57.9岁，CHD−组为59.7岁（p = 0.290）。在T0时：两组间激活素A相似（p = 0.724）；CHD+组患者的NT-proBNP较高（17 vs. 6 pmol/L，p = 0.016），曲线下面积（AUC）为0.84，最佳截断值为6.5 pmol/L。在T1时：CHD+组患者的激活素A较高（0.65 vs. 0.38 ng/mL，p = 0.045），AUC为0.62，无最佳截断值。CHD+组患者的NT-pro-BNP较高（63 vs. 11 pmol/L，p < 0.001），AUC为0.89，最佳截断值为27 pmol/L。各组间血清素（p = 0.345）、sST2（p = 0.867）和CTGF（p = 0.232）水平相似。这项大型验证研究确定NT-proBNP是CHD的最佳生物标志物。血清素水平升高且NT-proBNP水平在6.5至27 pmol/L之间，特别是>27 pmol/L的患者，应密切监测CHD的发生。
