Elevated systemic levels of the matrix metalloproteinase inhibitor TIMP-1 correlate with clinical markers of cachexia in patients with chronic pancreatitis and pancreatic cancer

• Published in: BMC cancer 2018-02, Vol.18 (1), p.128-128, Article 128
• Main Authors: Prokopchuk, Olga, Grünwald, Barbara, Nitsche, Ulrich, Jäger, Carsten, Prokopchuk, Oleksii L, Schubert, Elaine C, Friess, Helmut, Martignoni, Marc E, Krüger, Achim
• Format: Article
• Language: English
• Subjects: Cachexia; Cachexia biomarker; Development and progression; Diagnosis; Enzyme-linked immunosorbent assay; Health aspects; Jaundice; Pancreas; Pancreatic cancer; Pancreatitis; Prognosis; TIMP-1
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4055-9

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a candidate diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). Here, we determined the possible association of systemic TIMP-1 levels with cachexia and jaundice, two common PDAC-associated conditions. Plasma TIMP-1 was measured by ELISA in patients diagnosed with PDAC (n = 36) and chronic pancreatitis (CP) (n = 25). Patients without pancreatic pathologies and known malignancies of other origin served as controls (n = 13). TIMP-1 levels in these patients were tested for asscociation with jaundice and chachexia, and furthermore correlated with cachexia-related clinical parameters such as weight loss and ferritin, parameters of lung function, hemoglobin and liver synthesis parameters. TIMP-1 plasma levels were mostly higher in CP and PDAC patients with concomitant jaundice or cachexia. Elevated plasma TIMP-1 levels were also associated with clinical cachexia markers, including absolute and relative values of weight loss and lung function, as well as ferritin, hemoglobin, and cholinesterase levels. TIMP-1 levels significantly correlated with cachexia only in patients without jaundice. Jaundice also impaired the use of TIMP-1 as a prognostic marker in cancer patients. Relating to cachexia status alone, a slightly improved association of TIMP-1 levels with survival of PDAC patients was observed. This retrospective study reports for the first time that plasma levels of TIMP-1 are associated with pancreatic lesion-induced cachexia in patients without jaundice. TIMP-1 is counterindicated as a survival marker in patients with jaundice.