Abstract
Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and one of the deadliest diseases overall. New biomarkers are urgently needed to allow early diagnosis, one of the only factors that currently improves prognosis. Here we analyzed whether the detection of circulating galectin-1 (Gal-1), a soluble carbohydrate-binding protein overexpressed in PDA tissue samples, can be used as a biomarker for PDA. Gal-1 levels were determined by ELISA in plasma from healthy controls and patients diagnosed with PDA, using three independent cohorts. Patients with chronic pancreatitis (CP) were also included in the study to analyze the potential of Gal-1 to discriminate between cancer and inflammatory process. Plasma Gal-1 levels were significantly increased in patients with PDA as compared to controls in all three cohorts. Gal-1 sensitivity and specificity values were similar to that of the CA19-9 biomarker (the only FDA-approved blood test biomarker for PDA), and the combination of Gal-1 and CA19-9 significantly improved their individual discriminatory powers. Moreover, high levels of Gal-1 were associated with lower survival in patients with non-resected tumors. Collectively, our data indicate a strong potential of using circulating Gal-1 levels as a biomarker for detection and prognostics of patients with PDA.
Highlights
Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and presents the worst prognosis of all tumors
Gal-1 was highly expressed by pancreatic stellate cells/ fibroblasts associated with desmoplasia in chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN), low- or high-grade pancreatic intraepithelial neoplasia (PanINs) and PDA, but it was not detected in ductal cells in any tissue samples (Figure 1A and Supplementary Table 1)
We found that Gal-1 levels increased in patients with CP as compared to controls (BarcelonaHM, 34.17 ng/ml compared to 21.62 ng/ml; LiverpoolUL, 20.34 ng/ml compared to 17.10 ng/ml), significance was only reached for Barcelona-Hospital del Mar (HM) (Figure 2 and Table 1)
Summary
Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and presents the worst prognosis of all tumors. It is currently the fourth leading cause of cancer-related deaths in Western countries and is predicted to rise to the second by 2030 [1]. The most accepted model for PDA progression is that tumors arise through the progressive accumulation of genetic alterations in normal cells, starting with non-invasive precursor lesions called pancreatic intraepithelial neoplasia (PanINs) and ending with infiltrating ductal adenocarcinoma [2]. Pancreatic inflammation accelerates PDA initiation and progression in mouse models of this disease [7]. As both PDA and CP initially display similar vague symptoms, such as abdominal pain, digestive symptoms, weight loss and inflammation, differential diagnosis between both diseases is very difficult at early stages—yet early diagnosis is crucial for treatment of PDA
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