Combination of procalcitonin, C‑reaction protein and carcinoembryonic antigens for discriminating between benign and malignant pleural effusions

Ji,Mingde; Zhu,Xiaofei; Dong,Jie; Qian,Shining; Meng,Fei; Gu,Wanjian; Qiu,Wen

doi:10.3892/ol.2018.8871

Combination of procalcitonin, C‑reaction protein and carcinoembryonic antigens for discriminating between benign and malignant pleural effusions

Authors:
- Mingde Ji
- Xiaofei Zhu
- Jie Dong
- Shining Qian
- Fei Meng
- Wanjian Gu
- Wen Qiu
View Affiliations

Affiliations: Department of Laboratory Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China, Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: June 1, 2018 https://doi.org/10.3892/ol.2018.8871
Pages: 1727-1735
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pleural effusion (PE) is a common manifestation associated with certain chest diseases. However, there is no effective diagnostic marker with high sensitivity and specificity. The aim of the present study was to evaluate the diagnostic performance of several biomarkers in the use of detecting malignant pleural disorder. One hundred and fifty patients with a specific diagnosis of exudative PE were enrolled in this study and were divided into the benign PE group (n=93) and the malignant PE group (n=57). Thoracoscopy was conducted to identify the reasons for the PE. Biomarkers in pleural fluid and in sera were determined either by microparticle enzyme immunoassay [carcinoembryonic antigen (CEA)], fluorescence immunoassay [procalcitonin (PCT)] or light‑scattering turbidimetric immunoassay [C‑reaction protein (CRP)]. Then, correlation analysis and receiver‑operating characteristic (ROC) curve analysis individually or in combination were performed. The CRP and PCT levels were higher in benign PE than they were in malignant PE (PCT: P=0.017, P=0.032; CRP: P=0.001, P<0.001, respectively), while CEA levels were lower in benign PE than in malignant PE (CEA: P=0.001, P=0.001, respectively). During the ROC curve analysis, an optimal discrimination was identified by combining pleural CRP, pleural CEA and serum (s)PCT with an area under the curve of 0.973 (sensitivity, 98.9%; specificity, 89.5%). In the diagnosis of PE, there was no single biomarker that appeared to be adequately accurate. The combination of pleural CRP, pleural CEA and sPCT may represent an efficient diagnostic procedure for guiding the patient towards follow‑up clinical treatment.

View Figures

View References

1	Braunschweig T, Chung JY, Choi CH, Cho H, Chen QR, Xie R, Perry C, Khan J and Hewitt SM: Assessment of a panel of tumor markers for the differential diagnosis of benign and malignant effusions by well-based reverse phase protein array. Diagn Pathol. 10:532015. View Article : Google Scholar : PubMed/NCBI
2	Maskell NA and Butland RJ; Pleural Diseases Group, Standards of Care Committee, British Thoracic Society: BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax. 58(Suppl 2): ii8–ii17. 2003. View Article : Google Scholar : PubMed/NCBI
3	Yoon DW, Cho JH, Choi YS, Kim J, Kim HK, Zo JI and Shim YM: Predictors of survival in patients who underwent video-assisted thoracic surgery talc pleurodesis for malignant pleural effusion. Thorac Cancer. 7:393–398. 2016. View Article : Google Scholar : PubMed/NCBI
4	Porcel JM, Vives M, Esquerda A, Salud A, Pérez B and Rodríguez-Panadero F: Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest. 126:1757–1763. 2004. View Article : Google Scholar : PubMed/NCBI
5	Catarino PA and Goldstraw P: The future in diagnosis and staging of lung cancer: Surgical techniques. Respiration. 73:717–732. 2006. View Article : Google Scholar : PubMed/NCBI
6	Gu P, Huang G, Chen Y, Zhu C, Yuan J and Sheng S: Diagnostic utility of pleural fluid carcinoembryonic antigen and CYFRA 21-1 in patients with pleural effusion: A systematic review and meta-analysis. J Clin Lab Anal. 21:398–405. 2007. View Article : Google Scholar : PubMed/NCBI
7	Liang QL, Shi HZ, Qin XJ, Liang XD, Jiang J and Yang HB: Diagnostic accuracy of tumour markers for malignant pleural effusion: A meta-analysis. Thorax. 63:35–41. 2008. View Article : Google Scholar : PubMed/NCBI
8	Ryu JS, Lee HJ, Cho JH, Han HS and Lee HL: The implication of elevated carcinoembryonic antigen level in pleural fluid of patients with non-malignant pleural effusion. Respirology. 8:487–491. 2003. View Article : Google Scholar : PubMed/NCBI
9	Alataş F, Alataş O, Metintaş M, Colak O, Harmanci E and Demir S: Diagnostic value of CEA, CA 15-3, CA 19-9, CYFRA 21-1, NSE and TSA assay in pleural effusions. Lung Cancer. 31:9–16. 2001. View Article : Google Scholar : PubMed/NCBI
10	Villena V, López-Encuentra A, Echave-Sustaeta J, Martín-Escribano P, Ortuño-de-Solo B and Estenoz-Alfaro J: Diagnostic value of CA 549 in pleural fluid. Comparison with CEA, CA 15.3 and CA 72.4. Lung Cancer. 40:289–294. 2003.
11	Shitrit D, Zingerman B, Shitrit AB, Shlomi D and Kramer MR: Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: Analysis of 116 cases and review of the literature. Oncologist. 10:501–507. 2005. View Article : Google Scholar : PubMed/NCBI
12	Lee JH and Chang JH: Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer. Chest. 128:2298–2303. 2005. View Article : Google Scholar : PubMed/NCBI
13	Mehanic S and Baljic R: The importance of serum procalcitonin in diagnosis and treatment of serious bacterial infections and sepsis. Mater Sociomed. 25:277–281. 2013. View Article : Google Scholar : PubMed/NCBI
14	Uzzan B, Cohen R, Nicolas P, Cucherat M and Perret GY: Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: A systematic review and meta-analysis. Crit Care Med. 34:1996–2003. 2006. View Article : Google Scholar : PubMed/NCBI
15	Nijsten MW, Olinga P, The TH, de Vries EG, Koops HS, Groothuis GM, Limburg PC, ten Duis HJ, Moshage H, Hoekstra HJ, et al: Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 28:458–461. 2000. View Article : Google Scholar : PubMed/NCBI
16	Wacker C, Prkno A, Brunkhorst FM and Schlattmann P: Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis. Lancet Infect Dis. 13:426–435. 2013. View Article : Google Scholar : PubMed/NCBI
17	Brunkhorst R, Eberhardt OK, Haubitz M and Brunkhorst FM: Procalcitonin for discrimination between activity of systemic autoimmune disease and systemic bacterial infection. Intensive Care Med. 26(Suppl 2): S199–S201. 2000. View Article : Google Scholar : PubMed/NCBI
18	Joo K, Park W, Lim MJ, Kwon SR and Yoon J: Serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases. J Korean Med Sci. 26:1147–1151. 2011. View Article : Google Scholar : PubMed/NCBI
19	Buhaescu I, Yood RA and Izzedine H: Serum procalcitonin in systemic autoimmune diseases-where are we now? Semin Arthritis Rheum. 40:176–183. 2010. View Article : Google Scholar : PubMed/NCBI
20	Kim SE: Serum procalcitonin is a candidate biomarker to differentiate bacteremia from disease flares in patients with inflammatory bowel disease. Gut Liver. 10:491–492. 2016. View Article : Google Scholar : PubMed/NCBI
21	Wang CY, Hsiao YC, Jerng JS, Ho CC, Lai CC, Yu CJ, Hsueh PR and Yang PC: Diagnostic value of procalcitonin in pleural effusions. Eur J Clin Microbiol Infect Dis. 30:313–318. 2011. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Xie J, Guo F, Longhini F, Gao Z, Huang Y and Qiu H: Combination of C-reactive protein, procalcitonin and sepsis-related organ failure score for the diagnosis of sepsis in critical patients. Ann Intensive Care. 6:512016. View Article : Google Scholar : PubMed/NCBI
23	Izhakian S, Wasser WG, Fox BD, Vainshelboim B and Kramer MR: The diagnostic value of the pleural fluid C-reactive protein in parapneumonic effusions. Dis Markers. 2016:75397802016. View Article : Google Scholar : PubMed/NCBI
24	Xu C, Yu L, Zhan P and Zhang Y: Elevated pleural effusion IL-17 is a diagnostic marker and outcome predictor in lung cancer patients. Eur J Med Res. 19:232014. View Article : Google Scholar : PubMed/NCBI
25	Antonangelo L, Sales RK, Corá AP, Acencio MM, Teixeira LR and Vargas FS: Pleural fluid tumour markers in malignant pleural effusion with inconclusive cytologic results. Curr Oncol. 22:e336–e341. 2015. View Article : Google Scholar : PubMed/NCBI
26	Li H, Huang L, Tang H, Zhong N and He J: Pleural fluid carcinoembryonic antigen as a biomarker for the discrimination of tumor-related pleural effusion. Clin Respir J. 11:881–886. 2017. View Article : Google Scholar : PubMed/NCBI
27	Gaspar MJ, de Miguel J, García Díaz JD and Díez M: Clinical utility of a combination of tumour markers in the diagnosis of malignant pleural effusions. Anticancer Res. 28:2947–2952. 2008.PubMed/NCBI
28	Molina R, Bosch X, Auge JM, Filella X, Escudero JM, Molina V, Solé M and López-Soto A: Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site. Tumour Biol. 33:463–474. 2012. View Article : Google Scholar : PubMed/NCBI
29	Miédougé M, Rouzaud P, Salama G, Pujazon MC, Vincent C, Mauduyt MA, Reyre J, Carles P and Serre G: Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions. Br J Cancer. 81:1059–1065. 1999. View Article : Google Scholar : PubMed/NCBI
30	Blasi F, Stolz D and Piffer F: Biomarkers in lower respiratory tract infections. Pulm Pharmacol Ther. 23:501–507. 2010. View Article : Google Scholar : PubMed/NCBI
31	Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D and Sgarbi L: Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care. 8:R234–R242. 2004. View Article : Google Scholar : PubMed/NCBI
32	Meidani M, Khorvash F, Abolghasemi H and Jamali B: Procalcitonin and quantitative C-reactive protein role in the early diagnosis of sepsis in patients with febrile neutropenia. South Asian J Cancer. 2:216–219. 2013. View Article : Google Scholar : PubMed/NCBI
33	Magrini L, Travaglino F, Marino R, Ferri E, de Berardinis B, Cardelli P, Salerno G and Di Somma S: Procalcitonin variations after Emergency Department admission are highly predictive of hospital mortality in patients with acute infectious diseases. Eur Rev Med Pharmacol Sci. 17(Suppl 1): S133–S142. 2013.