Abstract
BackgroundTissue 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.MethodsPlasma 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.ResultsTIMP-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.ConclusionThis 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.
Highlights
Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a candidate diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC)
TIMP1 signaling via CD63 leads to activation of hepatic stellate cells, which create a pre-metastatic niche in the liver allowing efficient metastasis to this organ [14], and induces a tumor-promoting stress response in tumor cells [11]
We explore the impact of cachexia and jaundice on the diagnostic and prognostic value of TIMP-1, in chronic pancreatitis (CP) and PDAC
Summary
Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a candidate diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). Several independent studies have reported TIMP-1 to be of prognostic and diagnostic value for pancreatic ductal adenocarcinoma (PDAC) [15, 16]. TIMP-1 transcripts are found in both stroma and tumor cells of human PDAC [17]. TIMP-1 expression positively correlates with the degree of desmoplasia in the tumor stroma [17], as well as with de-differentiation of pancreatic tumor cells [18]. Plasma levels of TIMP-1 protein were found to be significantly elevated in PDAC and CP patients in an unbiased system-wide proteomics approach [20, 21], which further supports its potential usefulness as a diagnostic tumor marker
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