Biomarkers for pancreatic cancer: Recent achievements in proteomics and genomics through classical and multivariate statistical methods

Pancreatic cancer (PC) is one of the most aggressive and lethal neoplastic diseases. A valid alternative to the usual invasive diagnostic tools would certainly be the determination of biomarkers in peripheral fluids to provide less invasive tools for early diagnosis. Nowadays, biomarkers are generally investigated mainly in peripheral blood and tissues through high-throughput omics techniques comparing control vs pathological samples. The results can be evaluated by two main strategies: (1) classical methods in which the identification of significant biomarkers is accomplished by monovariate statistical tests where each biomarker is considered as independent from the others; and (2) multivariate methods, taking into consideration the correlations existing among the biomarkers themselves. This last approach is very powerful since it allows the identification of pools of biomarkers with diagnostic and prognostic performances which are superior to single markers in terms of sensitivity, specificity and robustness. Multivariate techniques are usually applied with variable selection procedures to provide a restricted set of biomarkers with the best predictive ability; however, standard selection methods are usually aimed at the identification of the smallest set of variables with the best predictive ability and exhaustivity is usually neglected. The exhaustive search for biomarkers is instead an important alternative to standard variable selection since it can provide information about the etiology of the pathology by producing a comprehensive set of markers. In this review, the most recent applications of the omics techniques (proteomics, genomics and metabolomics) to the identification of exploratory biomarkers for PC will be presented with particular regard to the statistical methods adopted for their identification. The basic theory related to classical and multivariate methods for identification of biomarkers is presented and then, the most recent applications in this field are discussed.