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 language | English |
|---|---|
| Article number | 717 |
| Journal | ecancermedicalscience |
| Volume | 11 |
| DOIs | |
| Publication status | Published - Jan 31 2017 |
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Keywords
- Circulating biomarker
- Early detection
- Non-small cell lung cancer
- Somatic mutation
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Circulating and tissue biomarkers in early-stage non-small cell lung cancer. / Fumagalli, Caterina; Bianchi, Fabrizio; Raviele, Paola Rafaniello; Vacirca, Davide; Bertalot, Giovanni; Rampinelli, Cristiano; Lazzeroni, Matteo; Bonanni, Bernardo; Veronesi, Giulia; Fusco, Nicola; Barberis, Massimo; Guerini-Rocco, Elena.
In: ecancermedicalscience, Vol. 11, 717, 31.01.2017.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85012890469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85012890469&partnerID=8YFLogxK
U2 - 10.3332/ecancer.2017.717
DO - 10.3332/ecancer.2017.717
M3 - Article
AN - SCOPUS:85012890469
VL - 11
JO - ecancermedicalscience
JF - ecancermedicalscience
SN - 1754-6605
M1 - 717
ER -