title: PRSS1 mutations and the proteinase/antiproteinase imbalance in the pathogenesis of pancreatic cancer.
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.
authors.affiliation: Department of Laboratory Medicine, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Department of Radiation Oncology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Qicai
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, the 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China. fengfang77777@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Surgery, the first Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian Province, China. Heqingliang89@sina.com.
authors.forename: Qingliang
authors.initials: Q
authors.lastname: He
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011487:Protein Conformation; D014357:Trypsin / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D000515:alpha 1-Antitrypsin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000515:alpha 1-Antitrypsin; C489303:PRSS1 protein, human; D014357:Trypsin
keywords: Enzyme kinetics; PRSS1 mutations; Pancreatic cancer; Serine proteinase; α1-antitrypsin