Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival

被引:45
作者
Quiros, RM
Rao, G
Plate, J
Harris, JE
Brunn, GJ
Platt, JL
Gattuso, P
Prinz, RA
Xu, XL
机构
[1] Rush Univ, Med Ctr, Dept Gen Surg, Chicago, IL 60612 USA
[2] Rush Univ, Med Ctr, Sect Med Oncol, Dept Med, Chicago, IL 60612 USA
[3] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA
[4] Mayo Clin, Dept Surg, Rochester, MN USA
[5] Mayo Clin, Dept Immunol, Rochester, MN USA
[6] Mayo Clin, Dept Pediat, Rochester, MN USA
[7] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA
关键词
heparanase-1; pancreatic adenocarcinoma; gemcitabine; PI-88;
D O I
10.1002/cncr.21648
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. It has previously been shown that heparanase-1 (HPR1), an endoglycosidase, is up-regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival. METHODS. Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme-linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan-Meier method, and their difference was evaluated by the log-rank test. A P value < 0.05 was considered statistically significant. RESULTS. The mean serum HPR1 activity in pancreatic carcinoma patients was 439 +/- 14 units/mL, compared with 190 +/- 4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1-positive tumors (660 +/- 62 units/mL) compared with those with HPR1-negative tumors (241 +/- 14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity > 300 units/mL was 7.9 +/- 0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity < 300 units/mL was 13.3 +/- 0.6 months. A Kaplan-Meier plot of the patient survival curve followed by log-rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine. CONCLUSIONS. Serum HPR1 activity in pancreatic carcinoma patients was found to be significantly elevated, in particular in those with HPR1-positive tumors. Increased serum HPR1 activity was associated with a shorter survival in patients with pancreatic carcinoma patients.
引用
收藏
页码:532 / 540
页数:9
相关论文
共 48 条
  • [1] New applications of gemcitabine and future directions in the management of pancreatic cancer
    Abbruzzese, JL
    [J]. CANCER, 2002, 95 (04) : 941 - 945
  • [2] Heparanase expression in invasive trophoblasts and acute vascular damage
    Dempsey, LA
    Plummer, TB
    Coombes, SL
    Platt, JL
    [J]. GLYCOBIOLOGY, 2000, 10 (05) : 467 - 475
  • [3] Platelet heparanase in vascular responses to xenotransplantation
    Dempsey, LA
    Plummer, TB
    Coombes, S
    Platt, JL
    [J]. TRANSPLANTATION PROCEEDINGS, 2000, 32 (05) : 972 - 972
  • [4] Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis
    Edovitsky, E
    Elkin, M
    Zcharia, E
    Peretz, T
    Vlodavsky, I
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (16): : 1219 - 1230
  • [5] El-Assal ON, 2001, CLIN CANCER RES, V7, P1299
  • [6] Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer
    Fairbanks, MB
    Mildner, AM
    Leone, JW
    Cavey, GS
    Mathews, WR
    Drong, RF
    Slightom, JL
    Bienkowski, MJ
    Smith, CW
    Bannow, CA
    Heinrikson, RL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (42) : 29587 - 29590
  • [7] A rapid quantitative assay for the detection of mammalian heparanase activity
    Freeman, C
    Parish, CR
    [J]. BIOCHEMICAL JOURNAL, 1997, 325 : 229 - 237
  • [8] Human platelet heparanase: purification, characterization and catalytic activity
    Freeman, C
    Parish, CR
    [J]. BIOCHEMICAL JOURNAL, 1998, 330 : 1341 - 1350
  • [9] Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma -: Evidence for its role in colonic tumorigenesis
    Friedmann, Y
    Vlodavsky, I
    Aingorn, H
    Aviv, A
    Peretz, T
    Pecker, I
    Pappo, O
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (04) : 1167 - 1175
  • [10] Heparan sulfate: growth control with a restricted sequence menu
    Gallagher, JT
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (03) : 357 - 361