Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients

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.

Symptoms related to gastrointestinal tract involvement and low muscularity in systemic sclerosis

“…The possible role of inflammation in the pathogenesis of muscle loss in SSc patients deserves speculation. Indeed, systemic inflammation is a potent driver of muscle loss in a number of both acute (e.g., ICU) and chronic (e.g., cancer) conditions [7,39,40]. In the present study, both the inflammatory indices CRP and ESR were not significantly different between the low and normal FFMI groups.…”

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

“…Mean circulating GDF-15 levels have been suggested to be higher in patients with pancreatic ductal adenocarcinoma, as 1731 pg/mL [ 23 ], 2428 [ 24 ], 7694.58 [ 1 ] and 2990.2 (this study), compared to patients with colorectal adenocarcinoma (CRC) (1371.0 pg/mL [ 23 ] and 2030 pg/mL [ 25 ]), non-small-cell lung carcinoma (mean, 1258.0 pg/mL [ 23 ] and median, 828.8–2000 pg/mL [ 34 , 35 ]), and gastric adenocarcinoma (1154.0 pg/mL [ 23 ]). An atlas of the human transcriptome reported that GDF-15 mRNA expression was relatively low in pancreatic cancer compared to prostate, urothelial, renal, melanoma, and colorectal cancers [ 36 ].…”

“…Our results showed that patients in the high-GDF-15 group experienced severe appetite loss compared with those in the low-GDF-15 group. In a previous study, median serum GDF-15 levels were higher in cancer patients with anorexia (1224.1 pg/mL) than in patients without anorexia (812.4 pg/mL) [ 34 ], where the cut-off value for anorexia was set at the lowest Functional Assessment of Anorexia/Cachexia Treatment (FAACT) score tertile, similar to the consensus definition of anorexia (FAACT ≤ 24) [ 38 ]. Our results showed that median MDASI scores in the high- and low-GDF-15 groups were 4 and 1 on a 0–10 scale, respectively.…”

Biomarkers for Cancer Cachexia: A Mini Review

“…However, association between GDF15 level and weight loss was only confirmed in patients with lung but not pancreatic cancer [ 33 ]. Additionally, another study found no difference in GDF15 levels between cancer patients with weight loss and those without weight change [ 35 ]. This study demonstrated an association between GDF15 levels and anorexia, suggesting that it could be an biomarker for anorexia rather than cachexia [ 35 ].…”