Background: The published circulating microRNA (miRNA) signatures proposed for earlystage non-small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of a miRNA simple signature of NSCLC are prerequisites for translation to clinical application. Methods: The serum level of miR-223 and miR-29c emerging from published studies, respectively as highly sensitive and highly specific biomarker of early-stage NSCLC, was measured with droplet digital PCR (ddPCR) technique in an Italian cohort of 75 stage I-II NSCLC patients and 111 tumor-free controls. By ROC curve analysis we evaluated the miR223 and miR-29c performance in discerning NSCLC cases from healthy controls. Results: Reproducibility and robust measurability of the two miRNAs using ddPCR was documented. In a training set (40 stage I-II NSCLCs; 56 controls), miR-223 and miR-29c respectively showed AUC of 0.753 (95% CI, 0.655-0.836) and 0.632 (95% CI, 0.527-0.729) in identifying NSCLC. Combination of miR-223 with miR-29c yielded an AUC of 0.750, not improved over that of miR-223 alone. Further, in an independent blind set (35 stage I-II NSCLCs; 55 controls), we validated serum miR-223 as effective biomarker of stage I-II NSCLC [AUC=0.808; 95% CI, 0.712-0.884)], confirming the miR-223 diagnostic performance reported by others in Chinese cohorts. Conclusions: Using ddPCR technology, miR-223 was externally validated as reproducible, effective serum biomarker of early-stage NSCLC in ethnically different subjects. Combination with miR-29c did not improve the miR-223 diagnostic performance. Impact: Serum miR-223 determination may be proposed as a tool for refining NSCLC risk stratification, independent of smoking habit and age

Serum miR-223: a validated biomarker for detection of early-stage non-small cell lung cancer

D'Antona, Paola;Cattoni, Maria;Dominioni, Lorenzo;Cinquetti, Raffaella;Gini, Elisabetta;Noonan, Douglas M;Imperatori, Andrea;Rotolo, Nicola;Campomenosi, Paola
2019-01-01

Abstract

Background: The published circulating microRNA (miRNA) signatures proposed for earlystage non-small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of a miRNA simple signature of NSCLC are prerequisites for translation to clinical application. Methods: The serum level of miR-223 and miR-29c emerging from published studies, respectively as highly sensitive and highly specific biomarker of early-stage NSCLC, was measured with droplet digital PCR (ddPCR) technique in an Italian cohort of 75 stage I-II NSCLC patients and 111 tumor-free controls. By ROC curve analysis we evaluated the miR223 and miR-29c performance in discerning NSCLC cases from healthy controls. Results: Reproducibility and robust measurability of the two miRNAs using ddPCR was documented. In a training set (40 stage I-II NSCLCs; 56 controls), miR-223 and miR-29c respectively showed AUC of 0.753 (95% CI, 0.655-0.836) and 0.632 (95% CI, 0.527-0.729) in identifying NSCLC. Combination of miR-223 with miR-29c yielded an AUC of 0.750, not improved over that of miR-223 alone. Further, in an independent blind set (35 stage I-II NSCLCs; 55 controls), we validated serum miR-223 as effective biomarker of stage I-II NSCLC [AUC=0.808; 95% CI, 0.712-0.884)], confirming the miR-223 diagnostic performance reported by others in Chinese cohorts. Conclusions: Using ddPCR technology, miR-223 was externally validated as reproducible, effective serum biomarker of early-stage NSCLC in ethnically different subjects. Combination with miR-29c did not improve the miR-223 diagnostic performance. Impact: Serum miR-223 determination may be proposed as a tool for refining NSCLC risk stratification, independent of smoking habit and age
2019
D'Antona, Paola; Cattoni, Maria; Dominioni, Lorenzo; Poli, Albino; Moretti, Francesca; Cinquetti, Raffaella; Gini, Elisabetta; Daffrè, Elisa; Noonan, ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2080949
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