Association between serum levels of soluble tumor necrosis factor receptors/CA 125 and disease progression in patients with epithelial ovarian malignancy

Abstract

BACKGROUND A prospective study was undertaken within the Gynecologic Oncology Group to determine whether serum levels of soluble tumor necrosis factor receptors I (sTNFR‐I) and II (sTNFR‐II), alone or in combination with CA 125, were associated with clinicopathologic characteristics or outcome in patients with epithelial ovarian malignancies. METHODS Quantitative immunoassays were performed on valid pretreatment serum specimens obtained from patients with epithelial ovarian malignancies to assess levels of sTNFR‐I, sTNFR‐II, and CA 125. The authors then analyzed the results of these immunoassays for potential correlations with clinicopathologic characteristics and outcome. RESULTS The median age of the 139 women evaluated was 59 years. Seventy‐eight percent had Stage III or IV disease, and 58% had serous carcinomas. sTNFR‐II was associated with age (P = 0.013), and CA 125 was associated with histologic subtype (P = 0.0009). In addition, sTNFR‐I (P = 0.037) and CA 125 (P < 0.0001) were associated with extent of disease. After adjusting for patient age, histologic subtype, and extent of disease, all three biomarkers were predictive of progression‐free survival, but not overall survival, when the combination was included in the model. The authors observed a 51% reduction (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.24–0.99), a 2.9‐fold increase (HR, 2.87; 95% CI, 1.15–7.20), and a 22% increase (HR, 1.22; 95% CI, 0.99–1.51) in the risk of progression for each unit increase in the log‐transformed levels of sTNFR‐I, sTNFR‐II, and CA 125, respectively. CONCLUSIONS The observations made in the current study—that among patients with low or high CA 125 levels, those with high sTNFR‐I levels and low sTNFR‐II levels had the lowest risk, that patients with low‐low or high‐high sTNFR‐I and sTNFR‐II levels, respectively, had an intermediate risk, and that patients with low sTNFR‐I levels and high sTNFR‐II levels had the highest risk of progression—suggested the potential value of simultaneous assessment of all three biomarkers in patients with epithelial ovarian malignancies. Cancer 2004. © 2004 American Cancer Society.

Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

“…Numerous reports have associated detection of abnormally high levels of TNF in the blood of epithelial ovarian cancer patients [7][8][9]. Within groups of patients with the same tumor type, higher levels of TNF-α correlated with advanced tumor stage and shorter survival time.…”

“…Several reports associated detection of abnormally high levels of TNF-α in the blood of ovarian cancer patients with a wide range of tumor types [7][8][9]. However, circulating TNF-α is not always detectable in cancer patients and can vary within individual patients over time and course of disease [10,11].…”

Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes – Findings from two community based cohorts of elderly

“…Several studies suggest an association between leukocyte activity and the occurrence of TNF receptors in serum, providing evidence that TNFR1 could constitute potent biomarkers for immunological cell responses, such as severe infections, transplantation-related complications as well as certain malignancies [27,28]. To exemplify, leukocyte cultures from breast cancer patients has been shown to secrete sTNFRs to a higher extent than cultures from healthy subjects, suggesting that the release of these molecules play a role in the immune systems native anti-tumor defense [29].…”

Translational research in the Gynecologic Oncology Group: Evaluation of ovarian cancer markers, profiles, and novel therapies

“…GOG 148 (Table 3) was a CTEP-sponsored, serum marker protocol by Burger and colleagues which demonstrated that among women who participated in a randomized phase III protocol for early stage EOC (GOG 95 or 157) or advanced stage EOC (GOG 111, 114, 132, 152 or 162) and had either low or high CA 125 levels, those with high sTNFR-I and low sTNFR-II levels had the lowest risk, patients with low sTNFR-I and sTNFR-II or high sTNFR-I and sTNFR-II levels had an intermediate risk, and patients with low sTNFR-I levels and high sTNFR-II levels had the highest risk of disease progression [16]. The prognostic value of serial assessment of these soluble death receptors in women with low and high CA125 is currently under investigation.…”