Differential diagnosis of pleural mesothelioma using Logic Learning Machine

BackgroundTumour markers are standard tools for the differential diagnosis of cancer. However, the occurrence of nonspecific symptoms and different malignancies involving the same cancer site may lead to a high proportion of misclassifications.Classification accuracy can be improved by combining information from different markers using standard data mining techniques, like Decision Tree (DT), Artificial Neural Network (ANN), and k-Nearest Neighbour (KNN) classifier. Unfortunately, each method suffers from some unavoidable limitations. DT, in general, tends to show a low classification performance, whereas ANN and KNN produce a "black-box" classification that does not provide biological information useful for clinical purposes.MethodsLogic Learning Machine (LLM) is an innovative method of supervised data analysis capable of building classifiers described by a set of intelligible rules including simple conditions in their antecedent part. It is essentially an efficient implementation of the Switching Neural Network model and reaches excellent classification accuracy while keeping low the computational demand.LLM was applied to data from a consecutive cohort of 169 patients admitted for diagnosis to two pulmonary departments in Northern Italy from 2009 to 2011. Patients included 52 malignant pleural mesotheliomas (MPM), 62 pleural metastases (MTX) from other tumours and 55 benign diseases (BD) associated with pleurisies. Concentration of three tumour markers (CEA, CYFRA 21-1 and SMRP) was measured in the pleural fluid of each patient and a cytological examination was also carried out.The performance of LLM and that of three competing methods (DT, KNN and ANN) was assessed by leave-one-out cross-validation.ResultsLLM outperformed all other considered methods. Global accuracy was 77.5% for LLM, 72.8% for DT, 54.4% for KNN, and 63.9% for ANN, respectively. In more details, LLM correctly classified 79% of MPM, 66% of MTX and 89% of BD. The corresponding figures for DT were: MPM = 83%, MTX = 55% and BD = 84%; for KNN: MPM = 58%, MTX = 45%, BD = 62%; for ANN: MPM = 71%, MTX = 47%, BD = 76%.Finally, LLM provided classification rules in a very good agreement with a priori knowledge about the biological role of the considered tumour markers.ConclusionsLLM is a new flexible tool potentially useful for the differential diagnosis of pleural mesothelioma.

[1]  Enrico Ferrari,et al.  Validation of a new multiple osteochondromas classification through Switching Neural Networks , 2013, American journal of medical genetics. Part A.

[2]  Marco Muselli,et al.  Use of Attribute Driven Incremental Discretization and Logic Learning Machine to build a prognostic classifier for neuroblastoma patients , 2014, BMC Bioinformatics.

[3]  S. Parodi,et al.  Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA , 2013, Medical Oncology.

[4]  Marco Muselli,et al.  Switching Neural Networks: A New Connectionist Model for Classification , 2005, WIRN/NAIS.

[5]  BMC Bioinformatics , 2005 .

[6]  H. Hoogsteden,et al.  The high post‐test probability of a cytological examination renders further investigations to establish a diagnosis of epithelial malignant pleural mesothelioma redundant , 2006, Diagnostic cytopathology.

[7]  J Espinosa Arranz,et al.  [Malignant mesothelioma]. , 1994, Medicina clinica.

[8]  G. Damonte,et al.  The application of atmospheric pressure matrix-assisted laser desorption/ionization to the analysis of long-term cryopreserved serum peptidome. , 2011, Analytical biochemistry.

[9]  H. Goike,et al.  Clinical utility of cytokeratins as tumor markers. , 2004, Clinical biochemistry.

[10]  Marco Muselli,et al.  Coupling Logical Analysis of Data and Shadow Clustering for Partially Defined Positive Boolean Function Reconstruction , 2011, IEEE Transactions on Knowledge and Data Engineering.

[11]  Marco Muselli,et al.  Extracting knowledge from biomedical data through Logic Learning Machines and Rulex , 2012 .

[12]  Hussein Hijazi,et al.  A classification framework applied to cancer gene expression profiles. , 2013, Journal of healthcare engineering.

[13]  S. Skates,et al.  Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma , 2007, Thorax.

[14]  Marco Muselli,et al.  Evaluating switching neural networks through artificial and real gene expression data , 2009, Artif. Intell. Medicine.

[15]  David J. Spiegelhalter,et al.  Machine Learning, Neural and Statistical Classification , 2009 .

[16]  K. Moons,et al.  Markers for the non-invasive diagnosis of mesothelioma: a systematic review , 2011, British Journal of Cancer.

[17]  M. Metintaş,et al.  Diagnostic value of CEA, CA 15-3, CA 19-9, CYFRA 21-1, NSE and TSA assay in pleural effusions. , 2001, Lung cancer.

[18]  S. Bielsa,et al.  Clinical impact and reliability of pleural fluid mesothelin in undiagnosed pleural effusions. , 2009, American journal of respiratory and critical care medicine.

[19]  Marco Muselli,et al.  Logic Learning Machine creates explicit and stable rules stratifying neuroblastoma patients , 2013, BMC Bioinformatics.

[20]  Vipin Kumar,et al.  Introduction to Data Mining , 2022, Data Mining and Machine Learning Applications.

[21]  D. Rice,et al.  Diagnosis, Staging, and Surgical Treatment of Malignant Pleural Mesothelioma , 2008, Current treatment options in oncology.

[22]  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.