A Novel Panel of Serum Biomarkers for MPM Diagnosis.

Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.

The regulatory roles of phosphatases in cancer.

The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3-kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies.

Characterization of novel 3'untranslated regions and related polymorphisms of the gene NPPC, encoding for the C-type natriuretic peptide.

Elevated plasmatic levels of C-type natriuretic peptide (CNP) were found in patients with chronic heart failure (CHF), but its use as sensitive and specific clinical bio-marker is still controversial. In fact, high levels of CNP were also observed in patients classified in low severity New York Heart Association (NYHA) classes. CNP is encoded by a gene poorly studied (NPPC, natriuretic-precursor peptide C), where the regulatory regions are not well defined and the role of single nucleotide polymorphisms (SNPs) poorly ascertained. In the present work, we focused on the characterization of the 3'untranslated region (3'UTR) of the gene, using Rapid Amplification of cDNA 3'-End (3' RACE), and we identified two novel transcript isoforms (L-3'UTR; S-3'UTR; accession number JF420840, HQ419060 respectively). Since it could be hypothesized that genetic variations could explain the observed inter-patients differences, we searched for novel SNPs, by the use of High Resolution Melting (HRM). The results showed a complete lack of genetic variations among our series of samples. Moreover, a preliminary evaluation, using literature information and bioinformatic prediction allowed us to predicted the putative relevant microRNAs binding to the novel 3'UTRs that could modulate the post-transcriptional regulation of NPPC and affect the plasmatic levels of CNP. We obtained 750 and 1024 predicted miRNAs targeting the S- and L-3'UTRs, respectively.