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

Zhang, Man; Li, Yan; Lippi, Giuseppe; Hu, Zhide

doi:10.21037/tlcr-20-1111

Cited by 34 publications

(59 citation statements)

References 138 publications

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“…Also, other tumor markers have been reported to be useful in lung cancer (such as CYFRA 21-1, NSE, or CR), which were not evaluated in this study. In addition, novel biomarkers, such as serum interleukin-27 (IL-27), gas chromatography-mass spectrometry (GC-MS) metabolomics, and serum reactive oxygen species modulator 1 (ROMO1), have been proposed as potential indexes for diagnosing lung cancer-associated MPE, but only a few were routinely detected in clinical practice (18,(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…The utility of biomarkers in the diagnosis of MPE has been studied extensively ( 16 , 18 ). Nonetheless, which biomarkers are the key to determining the diagnosis of MPE are yet controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, developing a method to accurately differentiate MPE from BPE at the earliest is highly desirable. The utility of biomarkers in the diagnosis of MPE has been studied extensively (16,18). Nonetheless, which biomarkers are the key to determining the diagnosis of MPE are yet controversial.…”

Section: Diagnostic Performance Of the Scoring System For Identifying Lung Cancer-associated Mpe And Tpementioning

confidence: 99%

“…Several biomarkers have been investigated for the identification of MPE and BPE in previous studies, such as adenosine deaminase (ADA), carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH) (16)(17)(18). However, no single marker from blood or PE could obtain both high sensitivity and specificity.…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram

Liang

Yuan

et al. 2021

Front. Oncol.

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BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Diagnostic Performance Of the Scoring System For Identifying Lung Cancer-associated Mpe And Tpementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram

Liang

Yuan

et al. 2021

Front. Oncol.

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“…The diagnosis of malignant pleural effusion is based on pleural effusion cytology and pleural biopsy as the gold standard. But there are disadvantages such as low sensitivity, invasiveness, and heavy reliance on the diagnostic experience of pathologists [4] . While the Mycobacterium tuberculosis culture technique, as the gold standard for the diagnosis of tuberculous pleural effusion, suffers from a low positivity rate and long culture time.…”

Section: Discussionmentioning

confidence: 99%

CEA and ADA in Pleural Fluid for Differential Malignant Pleural Effusion and Tuberculous Pleural Effusion

J¹,

Qi-Rui²

2021

Preprint

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Objective This study aimed to establish a predictive model based on the clinical manifestations and laboratory findings in pleural fluid of patients with pleural effusion for the differential diagnosis of malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE). Methods Clinical data and laboratory indices of pleural fluid were collected from patients with malignant pleural effusion and tuberculous pleural effusion in Zigong First People's Hospital between January 2019 and June 2020，and were compared between the two groups. Independent risk factors or Independent protective factors for malignant pleural effusion were investigated using multivariable logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of factors with independent effects, and combined diagnostic models were established based on two or more factors with independence effect. ROC curve was used to evaluate the diagnostic ability of each model, and the fit of the eath model was measured using Hosmer-Lemeshow goodness-of-fit test. Results Patients with MPE were older than those with TPE, the rate of fever of patients with MPE was lower than that of patients with TPE, and these differences were statistically significant (p < 0.05). Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin-19 fragment antigen (CYFRA21-1), cancer antigen 125 (CA125), and glucose (GLU) levels in the pleural fluid were higher, but total protein (TP), albumin (ALB) and Adenosine deaminase (ADA) levels in the pleural fluid were lower in MPE patients than in TPE patients, and the differences were statistically significant (P<0.05). In multivariate logistic regression analysis, CEA and NSE levels in the pleural fluid were independent risk factors for MPE, whereas ADA levels in pleural fluid and fever were independent protective factors for MPE. The differential diagnostic value of pleural fluid CEA and pleural fluid ADA for MPE and TPE were higher than that of pleural fluid NSE（p<0.05） and the area under the ROC curve was 0.901, 0.892, and 0.601, respectively. Four different binary logistic diagnostic models were established based on pleural fluid CEA combined with pleural fluid NSE, pleural fluid ADA or ( and ) fever. Among them, the model established with the combination of pleural fluid CEA and pleural fluid ADA (logit (P) = 0.513 + 0.457*CEA-0.101*ADA) had the highest diagnostic value for malignant pleural effusion, and its predictive accuracy was high with an area under the ROC curve of 0.968 [95% confidence interval (0.947, 0.988)]. But the diagnostic efficacy of the diagnostic model could not be improved by adding pleural fluid NSE and fever. Conclusion The model established with the combination of CEA and ADA in the pleural fluid has a high differential diagnostic value for malignant pleural effusion and tuberculous pleural effusion, and NSE in the pleural fluid and fever cannot improve the diagnostic efficacy of the diagnostic model.

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Single‐cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non‐small‐cell lung cancer

Zhang,

Wang,

Wen

et al. 2024

Clinical & Translational Med

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BackgroundRecurrent malignant pleural effusion (MPE) resulting from non‐small‐cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain.Methods16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non‐recurrent or recurrent MPE was determined after 3–6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single‐cell RNA sequencing (scRNA‐seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64).ResultsThe scRNA‐seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin‐4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal‐type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver‐gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non‐recurrent group, which was also associated with a trend towards worse overall survival (OS).ConclusionsCLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in‐depth mechanism studies on its biological function are warranted.Trial registrationNot applicable.

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

Cited by 34 publications

References 138 publications

Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram

Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram

CEA and ADA in Pleural Fluid for Differential Malignant Pleural Effusion and Tuberculous Pleural Effusion

Single‐cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non‐small‐cell lung cancer

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