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Published in: World Journal of Surgical Oncology 1/2017

Open Access 01-12-2017 | Research

Combining serum miRNAs, CEA, and CYFRA21-1 with imaging and clinical features to distinguish benign and malignant pulmonary nodules: a pilot study

Xianfeng Li et al.: Combining biomarker, imaging, and clinical features to distinguish pulmonary nodules

Authors: Xianfeng Li, Qinghua Zhang, Xiayun Jin, Lihua Cao

Published in: World Journal of Surgical Oncology | Issue 1/2017

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Abstract

Background

Our study was designed to improve the accuracy of determining whether pulmonary nodules are benign or malignant.

Methods

We evaluated the clinical and imaging features and serum markers: neuron specific enolase (NSE), carcino-embryonic antigen (CEA), cytokeratin fragment antigen 21–1 (CYFRA 21–1), miRNA-21-5p, and miR-574-5pof in 39 patients with pathology information. Factors that differed significantly between those with benign versus malignant pulmonary nodules were used to establish a prediction model for identifying malignant nodules.

Results

The studied nodules were 51.3% malignant and 48.7% benign. Age, smoking status, nodule diameter, history of emphysema, vascular sign, burr sign, CYFRA21-1, CEA, miRNA-21-5p, and miRNA-574-5p differed significantly between the benign and malignant nodule groups. Serum levels of CYRFA21-1 and CEA could be used to distinguish between malignant and benign nodules with a positive predictive value (PPV) of 80.0%, a negative predictive value (NPV) of 84.2%, and an area under the receiver operating characteristics curve (AUC) of 0.863. Using the serum levels of miRNA-21-5p and miRNA-574-5p, the PPV was 55%, the NPV was 84.2%, and the AUC was 0.797. When all four serum markers were combined, the PPV was 80%, the NPV was 89.5%, and the AUC was 0.921. We established a prediction model for malignant nodules, including clinical features, imaging features, and serum markers. In cross-validation, the ratio of discriminant conformance was 95%.

Conclusions

Serum levels of miRNA-21-5p and miRNA-574-5p are significantly higher in patients with malignant nodules than in patients with benign nodules and are potential serum biomarkers. Our prediction model could improve malignant nodule diagnosis.
Literature
1.
go back to reference Yang L, Yang G, Zhou M, Smith M, Ge H, Boreham J, Hu Y, Peto R, Wang J, Chen Z. Body mass index and mortality from lung cancer in smokers and nonsmokers: a nationally representative prospective study of 220,000 men in China. Int J Cancer. 2009;125:2136–43.CrossRefPubMed Yang L, Yang G, Zhou M, Smith M, Ge H, Boreham J, Hu Y, Peto R, Wang J, Chen Z. Body mass index and mortality from lung cancer in smokers and nonsmokers: a nationally representative prospective study of 220,000 men in China. Int J Cancer. 2009;125:2136–43.CrossRefPubMed
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
go back to reference Shen J, Liu Z, Todd NW, Zhang H, Liao J, Yu L, Guarnera MA, Li R, Cai L, Zhan M, Jiang F. Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer. 2011;11:374.CrossRefPubMedPubMedCentral Shen J, Liu Z, Todd NW, Zhang H, Liao J, Yu L, Guarnera MA, Li R, Cai L, Zhan M, Jiang F. Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer. 2011;11:374.CrossRefPubMedPubMedCentral
4.
go back to reference National Lung Screening Trial Research T, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.CrossRef National Lung Screening Trial Research T, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.CrossRef
5.
go back to reference Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105:10513–8.CrossRefPubMedPubMedCentral Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105:10513–8.CrossRefPubMedPubMedCentral
6.
go back to reference Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.CrossRefPubMed Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.CrossRefPubMed
7.
go back to reference Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, Shu YQ. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer. 2011;30:407–14.CrossRefPubMedPubMedCentral Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, Shu YQ. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer. 2011;30:407–14.CrossRefPubMedPubMedCentral
8.
go back to reference Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6:482–8.CrossRefPubMed Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6:482–8.CrossRefPubMed
9.
go back to reference Rivera MP, Mehta AC, Wahidi MM. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e191S–210.CrossRef Rivera MP, Mehta AC, Wahidi MM. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e191S–210.CrossRef
10.
go back to reference Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157:849–55.CrossRefPubMed Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157:849–55.CrossRefPubMed
11.
go back to reference Gould MK, Ananth L, Barnett PG, Veterans Affairs SCSG. A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules. Chest. 2007;131:383–8.CrossRefPubMedPubMedCentral Gould MK, Ananth L, Barnett PG, Veterans Affairs SCSG. A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules. Chest. 2007;131:383–8.CrossRefPubMedPubMedCentral
12.
go back to reference Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest. 2005;128:2490–6.CrossRefPubMed Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest. 2005;128:2490–6.CrossRefPubMed
13.
go back to reference Schultz EM, Sanders GD, Trotter PR, Patz Jr EF, Silvestri GA, Owens DK, Gould MK. Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules. Thorax. 2008;63:335–41.CrossRefPubMed Schultz EM, Sanders GD, Trotter PR, Patz Jr EF, Silvestri GA, Owens DK, Gould MK. Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules. Thorax. 2008;63:335–41.CrossRefPubMed
14.
go back to reference MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP, Patz Jr EF, Swensen SJ, Fleischner S. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. 2005;237:395–400.CrossRefPubMed MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP, Patz Jr EF, Swensen SJ, Fleischner S. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. 2005;237:395–400.CrossRefPubMed
15.
go back to reference Bekci TT, Senol T, Maden E. The efficacy of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen 15–3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in determining the malignancy of solitary pulmonary nodules. J Int Med Res. 2009;37:438–45.CrossRefPubMed Bekci TT, Senol T, Maden E. The efficacy of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen 15–3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in determining the malignancy of solitary pulmonary nodules. J Int Med Res. 2009;37:438–45.CrossRefPubMed
16.
go back to reference Chen Y, Stallings RL. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007;67:976–83.CrossRefPubMed Chen Y, Stallings RL. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007;67:976–83.CrossRefPubMed
17.
go back to reference Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 2005;204:280–5.CrossRefPubMed Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 2005;204:280–5.CrossRefPubMed
18.
go back to reference Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentral Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentral
19.
go back to reference Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2008;105:7269–74.CrossRefPubMedPubMedCentral Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2008;105:7269–74.CrossRefPubMedPubMedCentral
20.
go back to reference Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67:8433–8.CrossRefPubMed Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67:8433–8.CrossRefPubMed
21.
go back to reference Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed
22.
go back to reference Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.CrossRefPubMed Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.CrossRefPubMed
23.
go back to reference Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–93.CrossRefPubMed Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–93.CrossRefPubMed
24.
go back to reference Wei LI, Chen Y, Chen X. Diagnostic value of miRNA-21 and miRNA-155 expressions in pleuraleffusion. Jiangsu Med J. 2012;16:1882-84. Wei LI, Chen Y, Chen X. Diagnostic value of miRNA-21 and miRNA-155 expressions in pleuraleffusion. Jiangsu Med J. 2012;16:1882-84.
25.
go back to reference Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed
Metadata
Title
Combining serum miRNAs, CEA, and CYFRA21-1 with imaging and clinical features to distinguish benign and malignant pulmonary nodules: a pilot study
Xianfeng Li et al.: Combining biomarker, imaging, and clinical features to distinguish pulmonary nodules
Authors
Xianfeng Li
Qinghua Zhang
Xiayun Jin
Lihua Cao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2017
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-017-1171-y

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