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循环神经内分泌基因转录物 (NETest):一种用于早期识别胰腺神经内分泌肿瘤根治性手术疗效的术后策略。

Circulating Neuroendocrine Gene Transcripts (NETest): A Postoperative Strategy for Early Identification of the Efficacy of Radical Surgery for Pancreatic Neuroendocrine Tumors.

机构信息

Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Hospital Neuroendocrine Tumor Group (ENETS Center of Excellence), IRCCS San Raffaele Scientific Institute, "Vita-Salute San Raffaele" University, Via Olgettina 60, 20132, Milan, Italy.

Department of Pathology, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute San Raffaele" University, Via Olgettina 60, 20132, Milan, Italy.

出版信息

Ann Surg Oncol. 2020 Oct;27(10):3928-3936. doi: 10.1245/s10434-020-08425-6. Epub 2020 Apr 6.

Abstract

BACKGROUND

Surgery remains the only treatment for the cure of pancreatic neuroendocrine tumors (PanNETs). Biomarkers to identify the completeness of resection and predict recurrence are lacking.

OBJECTIVE

The aims of this study were to evaluate if the blood measurement of neuroendocrine gene transcripts (NETest) was diagnostic of PanNETs, and whether NETest blood levels could identify complete resection. We compared transcript analysis with the biomarker chromogranin A (CgA).

METHODS

This was a prospective, longitudinal, single-center study including 30 patients with a postoperative histological confirmation of PanNET. Blood for NETest and CgA was collected preoperatively and on postoperative day (POD) 1, POD5, and POD30. Transcripts were measured by real-time quantitative reverse transcription polymerase chain reaction and multianalyte algorithmic analysis (NETest; normal < 20), and CgA was measured by enzyme-linked immunosorbent assay (ELISA; normal < 109 ng/mL). Data are expressed as mean ± standard deviation (SD).

RESULTS

Pancreatic surgical resections (n = 30) were R0, 26; R1, 2; and R2, 2. Preoperatively, NETest score was elevated in all 30 patients (44.7 ± 27), but postoperatively, NETest scores significantly decreased (p = 0.006) to POD30 (24.7 ± 24). The proportion of patients (15/30) with an elevated score significantly decreased by POD30 (p < 0.0001). CgA levels were elevated preoperatively (184 ± 360 ng/mL) in only 9/30 patients, but did not decrease significantly postoperatively at POD30 (260 ± 589 ng/mL, p = 0.398). The number of patients with elevated CgA levels remained unchanged (9/30).

CONCLUSIONS

The NETest is an accurate diagnostic biomarker for PanNETs (100%). A decrease in NETest levels after radical resection suggests this blood test provides early assessment of surgical efficacy. CgA had no clinical utility.

摘要

背景

手术仍然是治愈胰腺神经内分泌肿瘤(PanNETs)的唯一方法。目前缺乏用于识别肿瘤切除完整性和预测复发的生物标志物。

目的

本研究旨在评估神经内分泌基因转录物(NETest)的血液测量是否对 PanNETs 具有诊断价值,以及 NETest 血液水平是否可以识别完全切除。我们比较了转录分析与生物标志物嗜铬粒蛋白 A(CgA)。

方法

这是一项前瞻性、纵向、单中心研究,纳入了 30 例术后组织学证实为 PanNET 的患者。在术前、术后第 1 天(POD1)、第 5 天(POD5)和第 30 天(POD30)采集 NETest 和 CgA 的血液样本。通过实时定量逆转录聚合酶链反应和多分析物算法分析(NETest;正常值<20)测量转录物,通过酶联免疫吸附测定(ELISA;正常值<109ng/mL)测量 CgA。数据以均数±标准差(SD)表示。

结果

胰腺外科手术(n=30)中,RO 切除 26 例,R1 切除 2 例,R2 切除 2 例。术前 30 例患者 NETest 评分均升高(44.7±27),但术后 NETest 评分显著降低(p=0.006)至 POD30(24.7±24)。POD30 时,有升高评分的患者比例(15/30)明显降低(p<0.0001)。术前仅 9/30 例患者 CgA 水平升高(184±360ng/mL),但术后 POD30 时 CgA 水平无明显下降(260±589ng/mL,p=0.398)。CgA 水平升高的患者数量保持不变(9/30)。

结论

NETest 是 PanNETs 的准确诊断生物标志物(100%)。根治性切除术后 NETest 水平下降提示该血液检测可早期评估手术疗效。CgA 无临床实用性。

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