No abstract

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.

No abstract

Malnutrition is highly common among cancer patients and is associated with a poor quality of life, increased treatment toxicities and decreased survival. The screening of malnutrition should be performed in an early stage of cancer disease and should be rapid, not expensive and highly sensitive to identify the risk of developing malnutrition. Importantly, international clinical guidelines suggest to perform screening for malnutrition in all cancer patients and if the risk is present, they recommend to perform a full nutritional assessment. During the screening phase, different nutritional parameters are considered including the loss of appetite, low food intake, body weight loss and burden of the disease. These items are present in several screening tools, such as the Nutrition Risk Screening (NRS)-2002, the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment (MNA) which represent the most widely used tools to screen for an altered nutritional status in cancer patients. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed an assessment tool for the diagnosis of malnutrition taking into account the presence of i) involuntary body weight loss, ii) body mass index, iii) low muscle mass, iv) low food intake and disease burden/inflammation; in particular, body weight loss, decreased body mass index (BMI), and low muscle mass are considered as phenotypic criteria, whereas reduced food intake, disease burden and inflammation are defined as etiologic criteria. To perform the diagnosis of malnutrition, GLIM consensus considered the presence of at least one phenotypic and one etiologic criterion. The above-mentioned screening tools were validated in different clinical settings and suggesting the use of one tool vs another is challenging considering, among others, different factors including the type and stage of cancer and the setting (i.e., inpatient or outpatient care). Recent data obtained among large cohorts of cancer patients indicate that personalized nutritional therapy reduced mortality risk and ameliorated quality of life and functionality among cancer patients with high nutritional risk, supporting the urgent need for implementing screening and diagnosis of malnutrition in this context.

We assessed the molecular phenotype of the browning of white adipose tissue in newly diagnosed cancer patients and controls undergoing surgery for gastrointestinal tumors and for non-malignant diseases, respectively. We collected subcutaneous adipose tissue (SAT) samples and using RT-PCR, we analyzed the expression of markers of browning and using Western blot the protein levels of UCP1 and PGC1α. The Ucp1 mRNA levels were lower in cancer patients vs. controls (p = 0.01), whereas Cidea and Tmem26 mRNA levels were higher in cancer patients. We found higher PGC1α protein levels in patients vs. controls, while no differences were seen for UCP1. The Ucp1 expression was lower in cachectic and non-cachectic patients vs. controls, whereas Cidea expression was higher in cachectic and non-cachectic patients vs. controls. Pgc1α mRNA levels were higher in cachectic vs. non-cachectic patients (p = 0.03) vs. controls (p = 0.016). According to type of tumors, we did not observe differences in Cidea expression, whereas Pgc1α was higher in pancreatic cancer vs. colorectal and vs. controls. We observed the lower expression of Ucp1 in pancreatic and colorectal cancer vs. controls. We documented higher UCP1 protein levels in pancreatic cancer patients vs. colorectal (p = 0.002) and vs. controls (p = 0.031). PGC1α protein levels were higher in pancreatic cancer patients vs. controls. Different markers of the browning of SAT are modulated, and pancreatic cancer showed changes in UCP1 and PGC1α; PGC1α was highly expressed in cachectic patients, with clinical implications that should be further clarified.