Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer

Annals of Surgical Oncology (Impact Factor: 4.12). 04/2012; 7(8):617-623. DOI: 10.1007/BF02725342

ABSTRACT 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.

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    Scandinavian Journal of Gastroenterology 01/2013; · 2.33 Impact Factor
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    ABSTRACT: The aim of this review is to summarize present evidence of an association between circulating levels of C-reactive protein (CRP) and cancer risk, and to evaluate whether elevated circulating CRP levels cause cancer. Additionally, the review provides background information on the acute-phase response, chronic inflammation, the molecular biology, function and measurement of CRP, circulating levels of CRP in health and disease, the principle of Mendelian randomization, the association between circulating levels of CRP and cancer prognosis, and cancer biomarkers. In the Copenhagen General Population Study of approximately 63,500 individuals, the distribution of circulating levels of CRP was markedly skewed to the right with 97% of the participants having CRP levels<10 mg/L. The median plasma CRP concentration was 1.53 mg/L (IQR, 1.14-2.51) and 34% of the participants had circulating CRP levels of ≥2 mg/L. Epidemiologic studies suggest that in patients with several types of solid cancers, elevated circulating levels of CRP are associated with poor prognosis, whereas in apparently healthy individuals from the general population, elevated levels of CRP are associated with increased future risk of cancer of any type, lung cancer, and possibly colorectal cancer, but not breast or prostate cancer. The robust association between circulating levels of CRP and cancer risk may be due to (1) causality: elevated CRP levels cause cancer, (2) reverse causality: occult cancer increases CRP levels, (3) or confounding: a third factor, e.g. inflammation, increases both CRP levels and the risk of cancer. Genetic epidemiologic studies (Mendelian randomization studies), which have examined the association between genetic polymorphisms influencing circulating levels of CRP and cancer risk suggest that circulating levels of CRP do not cause cancer. A lack of causality between elevated CRP levels and increased cancer risk does, however, not invalidate the potential clinical use of slightly increased CRP levels to predict risk of certain cancer types, and to improve staging and treatment allocation in patients diagnosed with cancer. Indeed, in a study of the general population, individuals with CRP levels in the highest versus the lowest quintile had a 1.3-fold increased risk of cancer of any type and a 2-fold increased risk of lung cancer. Among individuals diagnosed with cancer during the study period, individuals with a high baseline CRP (>3 mg/L) had an 80% greater risk of early death compared with those with low CRP levels (<1 mg/L). Accordingly, patients with invasive breast cancer and CRP levels>3 mg/L at diagnosis had a 1.7-fold increased risk of death from breast cancer compared to patients with CRP levels<1 mg/L at diagnosis.
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