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We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) ( p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) ( p = 0.049), severe appetite loss ( p = 0.011), and high serum levels of carbohydrate antigen 19-9 ( p = 0.019) and C-reactive protein ( p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK ( p = 0.007) and pAkt ( p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

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