Role of GSDMD and VEGF in differentiating between malignant and non-malignant pleural effusions

Beni-Suef University Journal of Basic and Applied Sciences - Tập 12 Số 1
Mai M. El-Kalashy1, Hanaa A. Eid1, Samah Awad2, Esraa Tawfik Allam2, Reham Ahmed Abdelaziz Hassan1, Amal A. El-Koa1
1Faculty of Medicine, Menoufia University, Menoufia, Egypt
2National Liver Institute, Menoufia University, Menoufia, Egypt

Tóm tắt

Abstract Background It is crucial to differentiate between benign and malignant pleural effusions while making a diagnosis. The purpose of this research was to investigate the diagnostic significance of GSDMD and VEGF in discriminating between different kinds of pleural effusion and their correlation with both progression-free and overall survivals in the malignant type. Methods Ninety-one pleural fluid samples, which were classified as transudates or exudates (tuberculous, para-infectious, or malignant) by pleural fluid classifications, were tested for GSDMD using sandwich ELIZA kits, and 41 of the exudative samples were randomly selected for VEGF testing. Both markers' diagnostic accuracy was assessed. Results The lowest level of GSDMD was associated with the transudate group (mean and SD of 2.35 ± 0.44 ng/mL) and the highest in the malignant effusion group (mean and SD of 4.38 ± 1.67 ng/mL). The specificity and sensitivity of GSDMD in the diagnosis of exudative PE were 97% and 98%, respectively (p = 0.001) with the cutoff point = 2.89). Regarding VEGF, its level was 222.3 ± 53.4 pg/ml for all studied samples where MPE (n = 21) was 261.2 ± 48.2 pg/ ml (mean ± SD), TBPE (n = 7) was 185.4 ± 6.96 pg/ml (mean ± SD), and PIPE (n = 13) was 179.3 ± 13.9 pg/ml (mean ± SD). The diagnostic accuracy of VEGF for the detection of MPE was 90% with a sensitivity of 100% and specificity of 80% and the cutoff point was 191.5 pg/ml. There were highly significant inverse correlations between progression-free survival and both GSDMD (r =− 0.531, p = 0.009) and VEGF (r = − 0.582, p = 0.006) in MPE. Conclusion Pleural effusion GSDMD can be an effective marker for differentiating the different kinds of PE, and VEGF levels can be a useful adjuvant marker in screening out MPE as a possible diagnosis, leading to the proper selection of patients who may benefit from more invasive procedures.

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Tài liệu tham khảo

Korczynski P et al (2009) Diagnostic utility of pleural fluid and serum markers in differentiation between malignant and non-malignant pleural effusions. Eur J Med Res 14(Suppl 4):128–133

Loddenkemper R (1998) Thoracoscopy–state of the art. Eur Respir J 11(1):213–221

Fiorelli A et al (2011) Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg 12(3):420–424

Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142

Pandeya A et al (2019) Gasdermin D (GSDMD) as a new target for the treatment of infection. Medchemcomm 10(5):660–667

Cheng KT et al (2017) Caspase-11–mediated endothelial pyroptosis underlies endotoxemia-induced lung injury. J Clin Investig 127(11):4124–4135

Gao J et al (2018) Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non-small cell lung cancer. Oncol Rep 40(4):1971–1984

Gong Z et al (2019) Regulation of host cell pyroptosis and cytokines production by Mycobacterium tuberculosis effector PPE60 requires LUBAC mediated NF-κB signaling. Cell Immunol 335:41–50

Zebrowski BK et al (1999) Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions. Clin Cancer Res 5(11):3364–3368

Light RW et al (1972) Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 77(4):507–513

Roth BJ, O’Meara TF, Cragun WH (1990) The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest 98(3):546–549

Eisenhauer EA et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247

Grove CS, Lee YC (2002) Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr Opin Pulm Med 8(4):294–301

Nishigaki Y et al (2003) Increased vascular endothelial growth factor in acute eosinophilic pneumonia. Eur Respir J 21(5):774–778

Maitre B et al (2001) Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J 18(1):100–106

Li P et al (2021) Pleural fluid GSDMD is a novel biomarker for the early differential diagnosis of pleural effusion. Front Microbiol 12:620322

Beckwith KS et al (2020) Plasma membrane damage causes NLRP3 activation and pyroptosis during mycobacterium tuberculosis infection. Nat Commun 11(1):2270

Derangère V et al (2014) Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells. Cell Death Differ 21(12):1914–1924

Jiang Z et al (2017) miRNA-214 inhibits cellular proliferation and migration in glioma cells targeting caspase 1 involved in pyroptosis. Oncol Res 25(6):1009–1019

Shi J et al (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660–665

Momi H et al (2002) Vascular endothelial growth factor and proinflammatory cytokines in pleural effusions. Respir Med 96(10):817–822

Sack U et al (2005) Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J 25(4):600–604

Duysinx BC et al (2008) Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions. Respir Med 102(12):1708–1714

Shu J et al (2007) Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions. Acta Oncol 46(7):1004–1011

Kaya A et al (2005) Vascular endothelial growth factor in benign and malignant pleural effusions. Arch Bronconeumol 41(7):376–379

Elia S et al (2008) Tumor type M2-pyruvate-kinase levels in pleural fluid versus plasma in cancer patients: a further tool to define the need for invasive procedures. Eur J Cardiothorac Surg 33(4):723–737

Ferrer J et al (2005) Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy. Chest 127(3):1017–1022

Cheng D, Kong H, Li Y (2013) Prognostic values of VEGF and IL-8 in malignant pleural effusion in patients with lung cancer. Biomarkers 18(5):386–390

Chen Y, Mathy NW, Lu H (2018) The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non-small cell lung cancer (Review). Mol Med Rep 17(6):8019–8030

Thickett D, Armstrong L, Millar A (1999) Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax 54(8):707–710

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Beni-Suef University Journal of Basic and Applied Sciences

Tập 12 Số 1

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