The utility of blood neuroendocrine gene transcript measurement in the diagnosis of bronchopulmonary neuroendocrine tumours and as a tool to evaluate surgical resection and disease progression†

Filosso, Pier Luigi; Kidd, Mark; Roffinella, Matteo; Lewczuk, Anna; Chung, Kyung-Min; Kolasińska-Ćwikła, Agnieszka; Ćwikła, Jarosław B.; Łowczak, Anna; Doboszyńska, Anna; Malczewska, Anna; Catalano, M.; Zunino, Valentina; Boita, Monica; Arvat, Emanuela; Cristofori, Riccardo; Guerrera, Francesco; Oliaro, A; Tesselaar, Margot E.T.; Buikhuisen, Wieneke A.; Kos–Kudła, Beata; Papotti, Mauro; Bodei, Lisa; Drozdov, Ignat; Modlin, Irvin M.

doi:10.1093/ejcts/ezx386

Cited by 39 publications

(87 citation statements)

References 26 publications

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“…This is consistent with previously reported data where the mean NETest was 48% in BPC and 6% in controls [17]. The AUROC for differentiating BPC from controls of 0.96 is comparable to the 0.98 previously reported [17].…”

Section: Discussionsupporting

confidence: 92%

“…The expression of a NET multigene signature has been demonstrated to be consistently detectable in the blood of BPC patients [16, 17]. The current study was designed to assess this observation and independently validate it in an independent cohort of European and North American individuals comprised of subjects from Poland, Italy, and the USA.…”

Section: Discussionmentioning

confidence: 83%

“…This is a separate patient cohort than the one previously reported [16, 17]. We calculated diagnostic accuracy and metrics (AUROC, sensitivity, and specificity) for the NETest in each group.…”

Section: Methodsmentioning

confidence: 99%

“…Transcripts (mRNA) were isolated from EDTA-collected whole blood samples (mini blood kit; Qiagen, Valencia, CA, USA), and real-time PCR was performed [20] (Fast Universal PCR Master Mix, Life Technologies). Target transcript levels are normalized and quantified versus a population control [17-19]. Final results are expressed as an activity index (NETest score) from 0 to 100% [17-19].…”

Section: Methodsmentioning

confidence: 99%

“…Target transcript levels are normalized and quantified versus a population control [17-19]. Final results are expressed as an activity index (NETest score) from 0 to 100% [17-19]. The upper limit of normal is 20.…”

Section: Methodsmentioning

confidence: 99%

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NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

et al. 2019

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Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript “liquid biopsy” (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25–0.31). Conclusions: Elevated NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 83%