Abstract
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.
Highlights
Tumour markers are standard tools for the differential diagnosis of cancer
soluble mesothelin-related peptide (SMRP) concentration was higher among Malignant pleural mesothelioma (MPM) than in the other two classes, whereas CYFRA 21-1 showed very low values among benign diseases (BD) and higher values among the two malignancies, with the highest median concentration observed for MPM
Logic Learning Machine (LLM) misclassified MPM patients with MTX and with BD approximately at the same rate, while MTX patients were more often misclassified with BD
Summary
Tumour markers are standard tools for the differential diagnosis of cancer. 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. Differential diagnosis of cancer plays a crucial role in addressing medical therapies and surgical interventions. Cancer diagnosis can become a very difficult task in the presence of nonspecific symptoms and different malignancies involving the same cancer site. The correct diagnosis of MPM is often hampered by the presence of atypical clinical symptoms that may cause misdiagnosis with either other malignancies (especially adenocarcinomas) or benign inflammatory or infectious diseases (BD) causing pleurisies [2]. In most cases a positive result from CE only does not allow to distinguish MPM from other malignancies [3]
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