Background: Magnesium (Mg) plays a central role in main cellular functions, acting as cofactors for more than 600 enzymes. In some neoplasias a low serum and a higher tissue Mg concentration was found, hypothesizing a high avidity for Mg of neoplastic tissue with a reduction of DNA reparing and an increase of metabolism and cell proliferation. On these basis many cellular Mg uptake antagonists are included in ongoing trials for anticancer therapies. Nowadays no data are available on Mg and hepatocellular carcinoma (HCC).
Aims: To compare serum and liver tissue Mg concentrations in patients with liver cirrhosis with and without HCC and to verify any changes in serum Mg with respect to the timing of HCC onset and tumor size.
Materials and Methods: The study will enroll 300 cirrhotic patients followed-up within an HCC surveillance program at the Department of Translational and Precision Medicine of Sapienza University of Rome, from 2001 to June 2018. For every patient will be retrieved demographic and clinical data regarding cirrhosis severity and evolution during the entire follow-up. For cirrhotic patients who developed HCC, will be considered date of HCC diagnosis, staging, HCC therapy and evolution. Serum Mg concentration will be retrieved from patients charts at each HCC surveillance visit, every 6 months. In cirrhotic patients who developed HCC, it will be particularly taken into consideration and compared serum Mg measured 6 months before the diagnosis of HCC, at diagnosis of HCC and during the subsequent follow-up.
HCC and cirrhotic liver tissue sampled 10 cm apart from the tumor (15 HCC patients) and cirrhotic tissue (15 non-HCC patients), collected at liver transplantation immediately after explantation, will be retrieved from formalin embedded samples for X-ray fluorescence (XRF) analysis. The analysis will be performed at Elettra Sincrotrone Trieste. In addition, 5 samples of healthy control liver obtained at surgery for cholecystectomy will be scanned.
No data are available in the literature on the serum and tissue magnesium concentration in hepatocellular carcinoma.
Clarifying the molecular pathogenesis of HCC and identifying accurate diagnostic markers. If we will demonstrate increased concentration of magnesium in hepatocellular carcinoma tissue, it would be possible to prospect new frontiers in defining therapeutic strategies for hepatocellular carcinoma. In particular, the demonstration of increased magnesium concentration eventually followed by that of aberrant expression/function of transient receptor potential melastatin 7 in hepatocellular carcinoma, would prompt to test natural or pharmacological transient receptor potential melastatin 7 antagonists to treat hepatocellular carcinoma as a single drug, in analogy to other tumors, or in association with mTOR inhibitors.