Abstract
This study aimed to investigate the mutations in the serine protease 1 gene (PRSS1) and the imbalance between trypsin and α1-antitrypsin in patients with pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the sequences of PRSS1 from 65 patients with pancreatic cancer and 260 healthy controls, direct sequencing was performed, and the clinical features were analyzed. In addition, enzyme-linked immunosorbent assay (ELISA) was employed to detect serum trypsin and α1-antitrypsin in pancreatic cancer patients and healthy controls in the same period. Mutations were found at the promoter and exon 3 of the PRSS1 in patients with pancreatic cancer. That is, five patients had c.410 C > T mutation causing p.Thr 137 Met, and three patients had c. −338 T > G mutation at the promoter of the PRSS1. In patients with PRSS1 mutations, serum trypsin was 34.5 ± 18.3 ng/mL, which was significantly higher than that in normal controls (10.65 ± 6.03 ng/mL) and other pancreatic cancer (28.61 ± 8.96 ng/mL). What is more, in pancreatic cancer patients, serum α1-antitrypsin was 1.69 ± 0.86 g/L, which was comparable to that in normal controls (1.55 ± 0.53 g/L), while the ratio of serum trypsin to α1-antitrypsin was 1.46-fold to normal controls. The results presented here have provided a greater insight into the PRSS1 mutations and proteinase-inhibitor interactions occurring in pancreatic cancer.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (81572442, 81571613, 81201362, 81201590, and 21275028) and financially supported by the Natural Science Foundation of Fujian Province (2013 J01302), Outstanding Youth Foundation of Fujian Provincial Higher Education (JA12133), and National High Technology Investigation Project Foundation of China (2012AA022604).
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Qiang Yi and Feng Dong contributed equally to this work.
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Yi, Q., Dong, F., Lin, L. et al. PRSS1 mutations and the proteinase/antiproteinase imbalance in the pathogenesis of pancreatic cancer. Tumor Biol. 37, 5805–5810 (2016). https://doi.org/10.1007/s13277-015-3982-1
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DOI: https://doi.org/10.1007/s13277-015-3982-1