NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.
Biomarker
Blood
Bronchopulmonary carcinoid
Lung cancer
NETest
Neuroendocrine tumor
PCR
Progression
Transcript
Journal
Neuroendocrinology
ISSN: 1423-0194
Titre abrégé: Neuroendocrinology
Pays: Switzerland
ID NLM: 0035665
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
10
2018
accepted:
22
12
2018
pubmed:
18
1
2019
medline:
18
12
2019
entrez:
18
1
2019
Statut:
ppublish
Résumé
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. To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. 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. 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). Elevated -NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.
Sections du résumé
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.
Identifiants
pubmed: 30654372
pii: 000497037
doi: 10.1159/000497037
pmc: PMC7472425
mid: NIHMS1622140
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
219-231Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2019 S. Karger AG, Basel.
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