Ricerc@Sapienza

Cachexia is a multifactorial condition which accompanies the development of cancer and cannot be completely reversed with conventional therapies. It occurs in about 80% of cancer patients and is the leading cause of death in about 22% of this population. The hallmark of cancer cachexia is the loss of muscle mass and the loss of white adipose tissue (WAT). The loss of WAT has been reported to be associated with reduced quality of life, worse outcomes and shorter survival in cancer. Considering that cachexia is highly prevalent during gastrointestinal (GI) cancer, we aim to i) analyze the changes in the morphological structure and composition of subcutaneous WAT in GI cancer patients with and without cachexia compared to non-cancer patients undergoing elective surgery for a non-neoplastic disease (controls); ii) analyze adipose tissue-specific miRNAs and the expression of proteins involved in the browning of WAT and in the lipolytic mechanisms in patients and controls; iii) analyze the changes in serum levels of pro-inflammatory cytokines, myokines and adipokines; iiii) evaluate the correlation between WAT modifications, the occurrence of skeletal muscle atrophy and the short and long-term complications and survival after abdominal surgery for cancer. We will enroll GI cancer patients with and without cachexia undergoing surgery and controls. We will collect adipose tissue during surgery to perform immunohistochemistry and morphological analysis of WAT, the occurrence of WAT browning by rt-PCR analysis (Eva1, Pdk4, Tmem26, Tbx1) and the expression of the proteins involved in browning and lipolysis of WAT by western blotting analysis (Tbx1,Cgi58, UCP1, PGC1-alfa, perilipin-1). The results of this project will provide useful indications on the biological and molecular mechanisms underlying the browning phenomenon and the WAT wasting during cancer cachexia, as well as their short and long-term prognostic value in a population of GI cancer patients.