However, particular significance could be ascribed to those proteins, showing a strong correlation with tumour development and progression. A fragment of MEP1A, a zincdependent metalloproteinases abundantly expressed in the apical membranes of renal proximal tubules was observed as over represented in ccRCC urine. It has been recently reported that MEP1A enzyme exhibits a broad expression pattern, implicating functions in angiogenesis, cancer, inflammation and fibrosis. Interestingly, a relevant pro-angiogenic activity has been described for this meprin with a molecular mechanism based on GDC-0449 proteolytic activation of pro-angiogenic growth factors, such as VEGF-A. Moreover, meprin a is reported to be expressed in several different tumours, as in breast and colorectal carcinomas and probably associated to the transition to malignant stages of colorectal carcinoma. However, its onco-expression is likely to be specific between different cancers, e.g. with quite low levels in ovarian cancer compared with gastrointestinal carcinomas. Finally, there is data indicating that meprins are involved in a complex with hypoxia-inducible factor-1a proposing a possible participation of these proteins in oxygen sensing mechanisms and in the response of the kidney proximal tubule cells to hypoxia process. Two different amino acid sequences have been recognized to give rise to the ccRCC discriminant signal observed at m/z 2192 in MALDI-LM spectra: a fragment of Probable G-protein coupled receptor 162 and a sequence derived from Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform. The first protein, is an orphan receptor assigned to G protein coupled receptors family involved in signal transmission. GPCRs are associated with several functions largely correlated to cancer such as cell proliferation, angiogenesis, tumour progression and development. Many GPCRs are over-expressed in various cancer types and they are constitutively active in malignant cells causing an aberrant response to various signals. The protein Phosphorylase b kinase regulatory subunit a is a key regulatory enzyme of glycogen metabolism. Glycogen can be broken down rapidly when glucose is needed, and Phosphorylase b kinase switches on another enzyme called glycogen phosphorylase b by converting it into the more active form, glycogen phosphorylase a. Alteration of KPB1 seems to be associated with muscle phosphorylase b kinase deficiency, a rare disorder caused by mutations in the gene coding for this protein. To our knowledge, whereas this protein certainly plays an important role in providing energy for cells, there is no evidence in literature that may explain a possible association with cancer. A fragment of OSTP was found in higher concentration in urine of malignant tumour patients. Several studies have shown its abundance both in tumour and tumour microenvironment cells.