Abstract

We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RARâ2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results: During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14-7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion: Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs.

Original languageEnglish
Article number717
Journalecancermedicalscience
Volume11
DOIs
Publication statusPublished - Jan 31 2017

Fingerprint

Sputum
Non-Small Cell Lung Carcinoma
Biomarkers
MicroRNAs
DNA
Neoplasms
Mutation
Neoplasm Genes
Telomerase
Chemoprevention
Tumor Biomarkers
Serum
Methylation
Real-Time Polymerase Chain Reaction
Lung

Keywords

  • Circulating biomarker
  • Early detection
  • Non-small cell lung cancer
  • Somatic mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Circulating and tissue biomarkers in early-stage non-small cell lung cancer",
abstract = "We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RAR{\^a}2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results: During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14-7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion: Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs.",
keywords = "Circulating biomarker, Early detection, Non-small cell lung cancer, Somatic mutation",
author = "Caterina Fumagalli and Fabrizio Bianchi and Raviele, {Paola Rafaniello} and Davide Vacirca and Giovanni Bertalot and Cristiano Rampinelli and Matteo Lazzeroni and Bernardo Bonanni and Giulia Veronesi and Nicola Fusco and Massimo Barberis and Elena Guerini-Rocco",
year = "2017",
month = "1",
day = "31",
doi = "10.3332/ecancer.2017.717",
language = "English",
volume = "11",
journal = "ecancermedicalscience",
issn = "1754-6605",
publisher = "Cancer Intellilgence",

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TY - JOUR

T1 - Circulating and tissue biomarkers in early-stage non-small cell lung cancer

AU - Fumagalli, Caterina

AU - Bianchi, Fabrizio

AU - Raviele, Paola Rafaniello

AU - Vacirca, Davide

AU - Bertalot, Giovanni

AU - Rampinelli, Cristiano

AU - Lazzeroni, Matteo

AU - Bonanni, Bernardo

AU - Veronesi, Giulia

AU - Fusco, Nicola

AU - Barberis, Massimo

AU - Guerini-Rocco, Elena

PY - 2017/1/31

Y1 - 2017/1/31

N2 - We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RARâ2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results: During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14-7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion: Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs.

AB - We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RARâ2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results: During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14-7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion: Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs.

KW - Circulating biomarker

KW - Early detection

KW - Non-small cell lung cancer

KW - Somatic mutation

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U2 - 10.3332/ecancer.2017.717

DO - 10.3332/ecancer.2017.717

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