Anorexia represents a common and debilitating symptom in patients with cancer, but its mechanism(s) are not completely understood. Lipocalin 2 (LCN2) is a pleiotropic mediator of inflammatory and metabolic processes that is secreted into circulation during diseases associated with wasting conditions, including cancer. It was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. In particular, LCN2 is increased in murine models of pancreatic cancer and its expression was associated with reduced food consumption. Interestingly, Lcn2 deletion was protective from anorexia and cachexia.
By the present project, we aim at evaluating primarily the association between LCN2 circulating levels and anorexia in different cohorts of cancer patients (gastrointestinal and lung) and in healthy controls; secondarily, we will assess the association(s) between LCN2 levels and body weight loss and with body composition changes in the same cohorts of patients. We will enroll lung and gastrointestinal (gastric, pancreatic and colorectal) cancer patients at their first oncology visit naïve to any anticancer treatments. We will collect data on nutritional status, i.e., current weight, usual weight and involuntary body weight loss in the previous 6 months. Anorexia will be assessed interviewing patients using specific appetite tools, including the FAACT questionnaire, which consists of 12 questions investigating different domains of anorexia, including the presence of nausea or vomiting. In cancer patients, we will analyze body composition by CT-scan (performed for cancer diagnosis and staging) calculating subcutaneous and visceral adipose tissue and the skeletal muscle index, as appropriate. LCN2 will be measured in sera of cancer patients and controls by ELISA kits.
The results of this project will provide important novel translational information on the role of LCN2 in the pathophysiology of cancer-associated anorexia.
Cancer-associated anorexia is a key component of sickness behavior and has been consistently shown to represent a negative prognostic factor in patients with chronic diseases. In particular, anorexia in cancer patients was shown to be associated with increased mortality with respect to non-anorexic patients. Moreover, anorexia is the main cause of low food intake (hypophagia) and bodyweight loss in cancer. In this light, investigation of factors mediating anorexia is pivotal to understand the pathophysiological basis of this phenomenon and possibly develop targeted therapeutic treatments. Recently, LCN2 was directly associated with anorexia in murine models of pancreatic cancer. Moreover, authors have analyzed LCN2 in patients with pancreatic cancer showing that LCN2 was associated with adipose and muscle wasting and increased mortality. They did not report data on appetite status of the patients studied.
By our project we aim to obtain novel evidences on LCN2 circulating levels in different types of cancer patients screened for the presence/absence of anorexia, adding insights on the role of LCN2 in the pathogenesis of impaired appetite during cancer.