Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer. The RANX05 Colorectal Cancer Study Group.
BACKGROUND
Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a prognostic variable in patients with colorectal cancer. It has been suggested, however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the acute-phase reactant C-reactive protein (CRP). In the present study we analyzed the association between plasma PAI-1 and serum CRP in patients scheduled for elective resection of colorectal cancer. In addition, the prognostic value of PAI-1 and CRP was studied in this patient cohort.


METHODS
PAI-1 and CRP were analyzed in citrated plasma and serum, respectively, obtained preoperatively from 594 patients. Patients who required preoperative blood transfusion received SAGM blood, in which soluble PAI-1 is not present. None of the patients received pre- or postoperative adjuvant chemotherapy, and all were followed in the outpatient clinic for at least 5 years or until death. The association of PAI-1 and CRP, respectively, with survival was tested using the median value of PAI-1 and the upper normal limit for CRP. Analyses were performed by inclusion of all patients, and in the subgroup of patients, who underwent curative resection.


RESULTS
The median follow-up period was 6.8 (5.4-7.9) years. The median value of plasma PAI-1 was 35.8 ng/ml, and values greater than 94 nmol/L identified patients with increased CRP levels. Comparison of the molecules showed that PAI-1 was weakly correlated with CRP (r = .26; P <.0001). Both molecules showed a Dukes independent distribution. In univariate survival analyses high levels of PAI-1 were found associated with poor prognosis and low levels with good prognosis (P = .02, HR: 1.3). Similarly, high levels of CRP were found associated with poor prognosis and low levels with good prognosis (P <.0001, HR: 1.9). In a multivariate statistical analysis including Dukes classification, gender, age, tumor location, perioperative blood transfusion, PAI-1 and CRP, plasma PAI-1 was a dependent prognostic variable, while serum CRP (P <.0001; HR: 1.4; 95% CI: 1.3-1.5) was found to be a Dukes independent prognostic variable. Similar analyses, excluding patients with Dukes' D disease showed serum CRP to be an independent prognostic variable (P <.0001; HR: 1.3: 95% CI: 1.2-1.5).


CONCLUSIONS
This study did not show a strong correlation between plasma PAI-1 and serum CRP in patients with colorectal cancer. Serum CRP was found to be a Dukes independent prognostic variable in this patient cohort, and was found to identify a subgroup of curatively resected patients at risk for short survival.
Nielsen
H J
HJ
Department of Surgical Gastroenterology, Hvidovre University Hospital, Denmark. h.j.nielsen@forum.dk
Christensen
I J
IJ
Sørensen
S
S
Moesgaard
F
F
Brünner
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011300:Preoperative Care; D011379:Prognosis; D011899:Ranitidine / Q000627:therapeutic use; D016019:Survival Analysis
D006635:Histamine H2 Antagonists; D017395:Plasminogen Activator Inhibitor 1; D011899:Ranitidine; D002097:C-Reactive Protein