A Novel Combination of Calprotectin and CXCL12 for Predicting Malignancy in Patients with Exudative Pleural Effusion

AbstractPleural effusion (PE) remains a significant challenge and public health problem, which needs novel noninvasive biomarkers for the precise diagnosis. The aim of this study was to further determine the clinical efficacy and diagnostic accuracy of a novel combination of calprotectin and CXCL12 for predicting malignancy in patients with exudative PE.Calprotectin and CXCL12 concentrations were measured in 95 individuals of exudative PE, with 39 malignant PE (MPE) and 56 benign PE (BPE). The accuracy of calprotectin and CXCL12 levels for discriminating MPE from BPE or tuberculous PE were evaluated using receiver-operating characteristic (ROC) curves. Univariate and multivariate logistic regression analyses were performed to test the association between calprotectin and CXCL12 levels and MPE.Calprotectin and CXCL12 levels of patients with MPE were significantly lower than that of BPE and tuberculous PE (P < 0.05). The area under the curve (AUC) of calprotectin and CXCL12 was 0.683 and 0.641 in MPE and BPE, and a combination of calprotectin ⩽500.19 ng/mL and CXCL12 ⩽6.11 ng/mL rendered a sensitivity and specificity of 48.72% and 78.57%, respectively. While in MPE and tuberculous PE, the AUC of calprotectin and CXCL12 was 0.696 and 0.690, and a combination of calprotectin ⩽421.73 ng/mL and CXCL12 ⩽3.71 ng/mL presented a sensitivity and specificity of 25.64% and 95.45%, respectively. Multivariate logistic regression demonstrated that both calprotectin and CXCL12 were independent predictors of MPE.Calprotectin and CXCL12 in pleural fluid are informative diagnostic biomarkers for predicting patients with MPE.

[1]  Richard G. White,et al.  The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets. , 2014, The lancet. Diabetes & endocrinology.

[2]  P. Stattin,et al.  High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome. , 2014, European journal of cancer.

[3]  Sajjad Karim,et al.  Impact of S100A8 expression on kidney cancer progression and molecular docking studies for kidney cancer therapeutics. , 2014, Anticancer research.

[4]  T. Ahmed,et al.  Pulmonary Tuberculosis in Severely-malnourished or HIV-infected Children with Pneumonia: A Review , 2013, Journal of health, population, and nutrition.

[5]  A. Musani,et al.  Malignant pleural effusions: a review. , 2013, Clinics in chest medicine.

[6]  A. Fernández-Villar,et al.  Calprotectin: a novel biomarker for the diagnosis of pleural effusion , 2012, British Journal of Cancer.

[7]  T. Kijima,et al.  CXCL12 as a biological marker for the diagnosis of tuberculous pleurisy. , 2012, Tuberculosis.

[8]  Clare Hooper,et al.  Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010 , 2010, Thorax.

[9]  M. P. Cadena,et al.  On the identification of biomarkers for non-small cell lung cancer in serum and pleural effusion. , 2010, Journal of proteomics.

[10]  J. Heffner,et al.  Diagnosis and management of malignant pleural effusions , 2007, Respirology.

[11]  E. Felip,et al.  Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures. , 2007, QJM : monthly journal of the Association of Physicians.

[12]  D. Foell,et al.  S100 proteins expressed in phagocytes: a novel group of damage‐associated molecular pattern molecules , 2007, Journal of leukocyte biology.

[13]  Shahin Rafii,et al.  S100 chemokines mediate bookmarking of premetastatic niches , 2006, Nature Cell Biology.

[14]  Hiroyuki Aburatani,et al.  Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis , 2006, Nature Cell Biology.

[15]  S. Benlloch,et al.  Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion , 2006, Cancer.

[16]  D. Mayer,et al.  S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. , 2006, Experimental cell research.

[17]  A. Wilkie,et al.  Fibroblast growth factor receptor 2, gain‐of‐function mutations, and tumourigenesis: investigating a potential link , 2005, The Journal of pathology.

[18]  David Shitrit,et al.  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. , 2005, The oncologist.

[19]  S. Cross,et al.  Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers , 2005, Histopathology.

[20]  W. Nacken,et al.  S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity , 2003, Microscopy research and technique.

[21]  Ravi Salgia,et al.  Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. , 2002, Cancer research.

[22]  F. Ottery,et al.  Integrating proactive nutritional assessment in clinical practices to prevent complications and cost. , 1998, Seminars in oncology.

[23]  J. Aparicio,et al.  Malignant Pleural Effusion: Prognostic Factors for Survival and Response to Chemical Pleurodesis in a Series of 120 Cases , 1998, Respiration.

[24]  E. Bruera ABC of palliative care: Anorexia, cachexia, and nutrition , 1997 .

[25]  T. Lyberg,et al.  Functional and clinical aspects of the myelomonocyte protein calprotectin. , 1997, Molecular pathology : MP.

[26]  T. Springer,et al.  A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) , 1996, The Journal of experimental medicine.

[27]  J. Sodroski,et al.  The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry , 1996, Nature.

[28]  T. Fahey,et al.  Nutritional support of the cancer patient , 1992, JPEN. Journal of parenteral and enteral nutrition.

[29]  U. Prakash,et al.  Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. , 1985, Mayo Clinic proceedings.

[30]  P. Cowen,et al.  Multiple pleural biopsy with the Abrams needle. , 1980, Thorax.

[31]  D. E. Dines,et al.  Pleural Effusion: A Diagnostic Dilemma , 1976 .

[32]  W. C. Ball,et al.  Pleural effusions: the diagnostic separation of transudates and exudates. , 1972, Annals of internal medicine.

[33]  S. S. Chaurasia,et al.  S100A proteins as molecular targets in the ocular surface inflammatory diseases. , 2014, The ocular surface.

[34]  Gang Huang,et al.  Diagnostic utility of pleural fluid carcinoembryonic antigen and CYFRA 21‐1 in patients with pleural effusion: a systematic review and meta‐analysis , 2007, Journal of clinical laboratory analysis.

[35]  E. Genofre,et al.  [Undiagnosed pleural effusion]. , 2006, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia.

[36]  A. Tarn,et al.  BTS guidelines for investigation of unilateral pleural effusion in adults. , 2004, Thorax.

[37]  J. Heffner,et al.  Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions. , 2000, Chest.

[38]  J. White,et al.  Differential chemotactic behavior of developing T cells in response to thymic chemokines. , 1998, Blood.

[39]  J. Fischer,et al.  Correlation of changes in brain indoleamine metabolism with onset of anorexia in rats. , 1982, American journal of surgery.

[40]  A. Schauffler A diagnostic dilemma. , 1968, Veterinary medicine, small animal clinician : VM, SAC.