A potential role for VEGF in the diagnostic approach of pleural effusions

Psatha, Aggeliki; Makris, Demosthènes; Kerenidi, Theodora; Daniil, Zoe; Kiropoulos, Theodoros; Gourgoulianis, Konstantinos

doi:10.21037/jtd.2016.05.73

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…Vascular endothelial growth factor (VEGF), which correlates strongly with abnormal angiogenesis 11 , has been shown to play a critical role in lung cancer 12 , and previous studies have applied VEGF to differential diagnoses among patients with chronic obstructive pulmonary disease and lung cancer, benign and malignant pleural fluid 13 . Notably, for patients with solitary pulmonary masses detected by chest radiography or CT screening, the levels of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid facilitate the differential diagnosis of primary lung cancer 14 .…”

Section: Introductionmentioning

confidence: 99%

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

Lai¹,

Wang²,

Zeng³

et al. 2018

J. Cancer

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Background: Effective biomarkers are essential to the differential diagnosis and severity assessment of non-small cell lung cancer (NSCLC). This study explored the use of the serum vascular endothelial growth factor (VEGF) levels as a biomarker with the aim of achieving better management of NSCLC.Methods: Serum VEGF levels were assayed via enzyme-linked immunosorbent assay in 180 patients with NSCLC, 136 patients with benign pulmonary nodules, and 119 healthy controls. We additionally detected the serum concentration of three traditional biomarkers—carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and cytokeratin 19 fragments (Cyfra 21-1)—to comparatively evaluate the efficiency and diagnostic value of VEGF in patients with NSCLC. We further evaluated the relationship between serum VEGF levels and clinicopathologic parameters. VEGF levels were compared between pro- and post-surgical patients using the Wilcoxon matched-pairs signed-rank test. DNA was isolated from the primary tumors. EGFR mutations were detected by Scorpions amplification refractory mutation system (ARMS).Results: Patients with NSCLC had significantly higher serum concentration of VEGF, compared to those with benign pulmonary nodules and healthy controls (P <0.0001). As a diagnostic biomarker of NSCLC, VEGF had area under the curve values of 0.824 and 0.839, sensitivities of 75.0% and 75.0%, and specificities of 93.3% and 95.6% when compared with healthy people and patients with benign pulmonary nodules, respectively; notably, these values were greater than those of CA125, Cyfra 21-1 and CEA. Furthermore, a model in which VEGF was combined with CEA, CA125, and Cyfra 21-1 was more effective for NSCLC diagnosis than VEGF alone (sensitivity, 85.0% and 84.4; specificity, 90.0% and 91.9% vs. healthy controls and patients with benign pulmonary nodules, respectively). When use to identify early-stage NSCLC, VEGF showed a better diagnostic efficacy than other biomarkers. The pro-surgical VEGF levels were significantly higher than those measured 25-30 days after surgery. Moreover, VEGF concentration differed significantly among cases according to TNM stages and malignant grades (P <0.0001). EGFR mutations and the size of benign pulmonary nodules did not affect the level of serum VEGF significantly.Conclusion: The serum VEGF levels exhibited relatively high sensitivity and specificity for NSCLC, and may therefore be a useful diagnostic biomarker. Furthermore, the serum VEGF levels could be used to assess prognosis and curative effects.

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Section: Introductionmentioning

confidence: 99%

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

Lai¹,

Wang²,

Zeng³

et al. 2018

J. Cancer

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“…Pleural effusion can be stimulated by various factors. Pleural fluid formation was shown to be associated with vascular endothelial growth factor (VEGF), which induces permeability of the pleural membrane [ 5 ], or associated with mast cells recruited by tumors to the pleural space through release of a matricellular protein osteopontin (OPN) in malignant effusion [ 6 ]. As mast cells also participate in host defense against MTB infection by regulating secretion of proinflammatory cytokines, which results in the attenuation of granuloma formation [ 7 ], they may have a role in pleural effusion during TB.…”

Section: Introductionmentioning

confidence: 99%

Secretion of IFN-γ Associated with Galectin-9 Production by Pleural Fluid Cells from a Patient with Extrapulmonary Tuberculosis

Zhao

Shiratori

Chagan-Yasutan

et al. 2017

IJMS

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In this study, we investigated the role of a matricellular protein galectin-9 (Gal-9) in pleural effusion related to tuberculosis (TB). Plasma and pleural fluid of a patient with extrapulmonary TB were analyzed for cytokine content by ELISA and Luminex. Peripheral blood mononuclear cells (PBMCs) and pleural fluid cells (PFCs) were examined for interferon-γ (IFN-γ) secretion by the enzyme-linked immunospot (ELISPOT) assay or IFN-γ ELISA, for apoptosis and necrosis by Cell Death Detection ELISA, and also underwent cell sorting. The results indicate that compared to plasma, pleural fluid had increased levels of IFN-γ (1.6 vs. 55.5 pg/mL), IL-10, IL-12p40, vascular endothelial growth factor (VEGF), and Gal-9 (3.0 vs. 936.0 pg/mL), respectively. PFCs culture supernatant exhibited higher concentration of Gal-9 compared to PBMCs in culture, consistent with enriched Gal-9 staining in the granuloma that is in closer vicinity to PFCs compared to PBMCs. PFCS displayed higher IFN-γ secretion after stimulation with TB antigens ESAT-6/CFP-10. Furthermore, in PFCs, Gal-9 alone could stimulate IFN-γ synthesis in culture or ELISPOT, which was inhibited by a Gal-9 antagonist lactose, and which may promote apoptosis and necrosis. These findings suggest that Gal-9 could modulate immune responses and participate in immunopathology of pleural effusion during TB.

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“…In 2012, a metaanalysis pooled the results of ten available studies, concluding that the diagnostic sensitivity and specificity of VEGF were 0.75 and 0.72, respectively (27). Some other studies on this topic have since been published (28)(29)(30)(31), so that an updated meta-analysis may be needed to re-assess the diagnostic accuracy of VEGF in MPE.…”

Section: Vascular Endothelial Growth Factor (Vegf) and Its Soluble Rementioning

confidence: 99%

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Zhang¹,

Li²,

Lippi³

et al. 2021

Transl Lung Cancer Res

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Although cytology and pleural biopsy of pleural effusion (PE) are the gold standards for diagnosing malignant pleural effusion (MPE), these tools' diagnostic accuracy is plagued by some limitations such as low sensitivity, considerable inter-observer variation and invasiveness. The assessment of PE biomarkers may hence be seen as an objective and non-invasive diagnostic alternative in MPE diagnostics. In this review, we summarize the characteristics and diagnostic accuracy of available PE biomarkers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigens 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), a fragment of cytokeratin 19 (CYFRA 21-1), chitinase-like proteins (CLPs), vascular endothelial growth factor (VEGF) and its soluble receptor, endostatin, calprotectin, cancer ratio, homocysteine, apolipoprotein E (Apo-E), B7 family members, matrix metalloproteinase (MMPs) and tissue-specific inhibitors of metalloproteinases (TIMPs), reactive oxygen species modulator 1 (Romo1), tumor-associated macrophages (TAMs) and monocytes, epigenetic markers (e.g., cell-free microRNA and mRNA). We summarized the evidence from systematic review and meta-analysis for traditional tumor markers' diagnostic accuracy. According to the currently available evidence, we conclude that the traditional tumor markers have high specificity (around 0.90) but low sensitivity (around 0.50). The diagnostic accuracy of novel tumor markers needs to be validated by further studies. None of these tumor biomarkers would have sufficient diagnostic accuracy to confirm or exclude MPE when used alone. A multi-biomarker strategy, also encompassing the use of artificial intelligence algorithms, may be a valuable perspective for improving the diagnostic accuracy of MPE.

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A potential role for VEGF in the diagnostic approach of pleural effusions

Cited by 6 publications

References 38 publications

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

Secretion of IFN-γ Associated with Galectin-9 Production by Pleural Fluid Cells from a Patient with Extrapulmonary Tuberculosis

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

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