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Published in: Respiratory Research 1/2020

01-12-2020 | Lung Cancer | Research

Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion

Authors: Hai Zhang, Changhui Li, Fang Hu, Xueyan Zhang, Yinchen Shen, Yuqing Chen, Feng Li

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio.

Patients and method

The study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators.

Result

In the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (all p < 0.001). In the test set, PF CEA at the cut-off value of 5.23 ng/ml showed the highest sensitivity, specificity and accuracy, positive and negative predictive value among other tumor biomarkers, which were 99.0%, 69.1%, 91.6%, 90.7%, and 95.9%, respectively.

Conclusion

PF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.
Appendix
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Literature
1.
go back to reference Wang S, Tian S, Li Y, Zhan N, Guo Y, Liu Y, et al. Development and validation of a novel scoring system developed from a nomogram to identify malignant pleural effusion. EBioMedicine. 2020;58:102924 ([published online ahead of print, 2020 Jul 30]). CrossRefPubMedPubMedCentral Wang S, Tian S, Li Y, Zhan N, Guo Y, Liu Y, et al. Development and validation of a novel scoring system developed from a nomogram to identify malignant pleural effusion. EBioMedicine. 2020;58:102924 ([published online ahead of print, 2020 Jul 30]). CrossRefPubMedPubMedCentral
2.
go back to reference Thompson JC, Fan R, Black T, Yu GH, Savitch SL, Chien A, et al. Measurement and immunophenotyping of pleural fluid EpCAM-positive cells and clusters for the management of non-small cell lung cancer patients. Lung Cancer. 2019;127:25–33. CrossRefPubMed Thompson JC, Fan R, Black T, Yu GH, Savitch SL, Chien A, et al. Measurement and immunophenotyping of pleural fluid EpCAM-positive cells and clusters for the management of non-small cell lung cancer patients. Lung Cancer. 2019;127:25–33. CrossRefPubMed
3.
go back to reference Feng M, Zhu J, Liang L, Zeng N, Wu Y, Wan C, et al. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis. Int J Clin Oncol. 2017;22(2):283–90. CrossRefPubMed Feng M, Zhu J, Liang L, Zeng N, Wu Y, Wan C, et al. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis. Int J Clin Oncol. 2017;22(2):283–90. CrossRefPubMed
4.
5.
go back to reference Hooper C, Lee YC, Maskell N, BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(Suppl 2):ii4-17. CrossRefPubMed Hooper C, Lee YC, Maskell N, BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(Suppl 2):ii4-17. CrossRefPubMed
6.
go back to reference Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet. 2003;361(9366):1326–30. CrossRefPubMed Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet. 2003;361(9366):1326–30. CrossRefPubMed
7.
go back to reference Menzies R, Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med. 1991;114(4):271–6. CrossRefPubMed Menzies R, Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med. 1991;114(4):271–6. CrossRefPubMed
8.
go back to reference Lombardi G, Zustovich F, Nicoletto MO, Donach M, Artioli G, Pastorelli D. Diagnosis and treatment of malignant pleural effusion: a systematic literature review and new approaches. Am J Clin Oncol. 2010;33(4):420–3. CrossRefPubMed Lombardi G, Zustovich F, Nicoletto MO, Donach M, Artioli G, Pastorelli D. Diagnosis and treatment of malignant pleural effusion: a systematic literature review and new approaches. Am J Clin Oncol. 2010;33(4):420–3. CrossRefPubMed
9.
go back to reference Noppen M. The utility of thoracoscopy in the diagnosis and management of pleural disease. Semin Respir Crit Care Med. 2010;31(6):751–9. CrossRefPubMed Noppen M. The utility of thoracoscopy in the diagnosis and management of pleural disease. Semin Respir Crit Care Med. 2010;31(6):751–9. CrossRefPubMed
10.
go back to reference Ferrer J, Villarino MA, Encabo G, Felip E, Bermejo B, Vilà S, et al. Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions. Cancer. 1999;86(8):1488–95. CrossRefPubMed Ferrer J, Villarino MA, Encabo G, Felip E, Bermejo B, Vilà S, et al. Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions. Cancer. 1999;86(8):1488–95. CrossRefPubMed
11.
go back to reference Mezger J, Calavrezos A, Drings P, Gatzemeier U, Kaukel E, Konietzko N, et al. Value of serum and effusion fluid CEA levels for distinguishing between diffuse malignant mesothelioma and carcinomatous pleural metastases. Lung. 1994;172(3):183–4. CrossRefPubMed Mezger J, Calavrezos A, Drings P, Gatzemeier U, Kaukel E, Konietzko N, et al. Value of serum and effusion fluid CEA levels for distinguishing between diffuse malignant mesothelioma and carcinomatous pleural metastases. Lung. 1994;172(3):183–4. CrossRefPubMed
12.
go back to reference Whitaker D, Shilkin KB, Stuckey M, Nieuwhof WN. Pleural fluid CEA levels in the diagnosis of malignant mesothelioma. Pathology. 1986;18(3):328–9. CrossRefPubMed Whitaker D, Shilkin KB, Stuckey M, Nieuwhof WN. Pleural fluid CEA levels in the diagnosis of malignant mesothelioma. Pathology. 1986;18(3):328–9. CrossRefPubMed
14.
15.
go back to reference Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol. 2014;50(5):161–5. CrossRefPubMed Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol. 2014;50(5):161–5. CrossRefPubMed
17.
go back to reference Tozzoli R, Basso SM, D’Aurizio F, Metus P, Lumachi F. Evaluation of predictive value of pleural CEA in patients with pleural effusions and histological findings: a prospective study and literature review. Clin Biochem. 2016;49(16–17):1227–31. CrossRefPubMed Tozzoli R, Basso SM, D’Aurizio F, Metus P, Lumachi F. Evaluation of predictive value of pleural CEA in patients with pleural effusions and histological findings: a prospective study and literature review. Clin Biochem. 2016;49(16–17):1227–31. CrossRefPubMed
18.
go back to reference Lee JH, 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. 2005;128(4):2298–303. CrossRefPubMed Lee JH, 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. 2005;128(4):2298–303. CrossRefPubMed
19.
go back to reference Hackbarth JS, Murata K, Reilly WM, Algeciras-Schimnich A. Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clin Biochem. 2010;43(13–14):1051–5. CrossRefPubMed Hackbarth JS, Murata K, Reilly WM, Algeciras-Schimnich A. Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clin Biochem. 2010;43(13–14):1051–5. CrossRefPubMed
20.
go back to reference Hackner K, Errhalt P, Handzhiev S. Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion. Ther Adv Med Oncol. 2019;11:1758835919850341. CrossRefPubMedPubMedCentral Hackner K, Errhalt P, Handzhiev S. Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion. Ther Adv Med Oncol. 2019;11:1758835919850341. CrossRefPubMedPubMedCentral
21.
go back to reference Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2012;76(2):138–43. CrossRefPubMed Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2012;76(2):138–43. CrossRefPubMed
22.
go back to reference Fu L, Wang R, Yin L, Shang X, Zhang R, Zhang P. CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: a meta-analysis. Int J Biol Markers. 2019;34(3):251–61. CrossRefPubMed Fu L, Wang R, Yin L, Shang X, Zhang R, Zhang P. CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: a meta-analysis. Int J Biol Markers. 2019;34(3):251–61. CrossRefPubMed
23.
go back to reference Wang L, Wang D, Zheng G, et al. Clinical evaluation and therapeutic monitoring value of serum tumor markers in lung cancer. Int J Biol Markers. 2016;31(1):e80–7. CrossRefPubMed Wang L, Wang D, Zheng G, et al. Clinical evaluation and therapeutic monitoring value of serum tumor markers in lung cancer. Int J Biol Markers. 2016;31(1):e80–7. CrossRefPubMed
24.
go back to reference Okamura K, Takayama K, Izumi M, Harada T, Furuyama K, Nakanishi Y. Diagnostic value of CEA and CYFRA 21–1 tumor markers in primary lung cancer. Lung Cancer. 2013;80(1):45–9. CrossRefPubMed Okamura K, Takayama K, Izumi M, Harada T, Furuyama K, Nakanishi Y. Diagnostic value of CEA and CYFRA 21–1 tumor markers in primary lung cancer. Lung Cancer. 2013;80(1):45–9. CrossRefPubMed
25.
go back to reference Rodrîguez-Panadero F, Borderas Naranjo F, López MJ. Pleural metastatic tumours and effusions. Frequency and pathogenic mechanisms in a post-mortem series. Eur Respir J. 1989;2(4):366–9. PubMed Rodrîguez-Panadero F, Borderas Naranjo F, López MJ. Pleural metastatic tumours and effusions. Frequency and pathogenic mechanisms in a post-mortem series. Eur Respir J. 1989;2(4):366–9. PubMed
27.
go back to reference Chen Z, Wang Y, Fang M. Analysis of tumor markers in pleural effusion and serum to verify the correlations between serum tumor markers and tumor size, TNM stage of lung adenocarcinoma. Cancer Med. 2020;9(4):1392–9. CrossRefPubMed Chen Z, Wang Y, Fang M. Analysis of tumor markers in pleural effusion and serum to verify the correlations between serum tumor markers and tumor size, TNM stage of lung adenocarcinoma. Cancer Med. 2020;9(4):1392–9. CrossRefPubMed
28.
go back to reference Psallidas I, Kalomenidis I, Porcel JM, Robinson BW, Stathopoulos GT. Malignant pleural effusion: from bench to bedside. Eur Respir Rev. 2016;25(140):189–98. CrossRefPubMed Psallidas I, Kalomenidis I, Porcel JM, Robinson BW, Stathopoulos GT. Malignant pleural effusion: from bench to bedside. Eur Respir Rev. 2016;25(140):189–98. CrossRefPubMed
Metadata
Title
Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion
Authors
Hai Zhang
Changhui Li
Fang Hu
Xueyan Zhang
Yinchen Shen
Yuqing Chen
Feng Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01557-z

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