PMID- 23468981 OWN - NLM STAT- MEDLINE DCOM- 20130910 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 2 DP - 2013 TI - Multiple marker detection in peripheral blood for NSCLC diagnosis. PG - e57401 LID - 10.1371/journal.pone.0057401 [doi] LID - e57401 AB - BACKGROUND: Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC). METHODS: 100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method. RESULTS: Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p=0.0002 and p=0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15-11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75-13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71-4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01-1.33; p=0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI=0.90-0.97, with sensitivity and specificity over 90%. CONCLUSIONS: Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer. FAU - Ulivi, Paola AU - Ulivi P AD - Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. p.ulivi@irst.emr.it FAU - Mercatali, Laura AU - Mercatali L FAU - Casoni, Gian-Luca AU - Casoni GL FAU - Scarpi, Emanuela AU - Scarpi E FAU - Bucchi, Lauro AU - Bucchi L FAU - Silvestrini, Rosella AU - Silvestrini R FAU - Sanna, Stefano AU - Sanna S FAU - Monteverde, Marco AU - Monteverde M FAU - Amadori, Dino AU - Amadori D FAU - Poletti, Venerino AU - Poletti V FAU - Zoli, Wainer AU - Zoli W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130226 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Biomarkers, Tumor) SB - IM MH - Aged MH - Biomarkers, Tumor/*blood MH - Carcinoma, Non-Small-Cell Lung/*blood MH - Case-Control Studies MH - Female MH - Humans MH - Lung Neoplasms/*blood MH - Male MH - Middle Aged MH - Real-Time Polymerase Chain Reaction PMC - PMC3582604 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/03/08 06:00 MHDA- 2013/09/11 06:00 PMCR- 2013/02/26 CRDT- 2013/03/08 06:00 PHST- 2012/11/05 00:00 [received] PHST- 2013/01/21 00:00 [accepted] PHST- 2013/03/08 06:00 [entrez] PHST- 2013/03/08 06:00 [pubmed] PHST- 2013/09/11 06:00 [medline] PHST- 2013/02/26 00:00 [pmc-release] AID - PONE-D-12-34055 [pii] AID - 10.1371/journal.pone.0057401 [doi] PST - ppublish SO - PLoS One. 2013;8(2):e57401. doi: 10.1371/journal.pone.0057401. Epub 2013 Feb 26.