Clinical value of selected markers of angiogenesis, inflammation, insulin resistance and obesity in type 1 endometrial cancer

Abstract

Background: It is a well-known fact show that the risk of developing endometrial cancer (type 1 EC) is strongly associated with obesity. In this study, selected markers, such as obesity, insulin resistance, angiogenesis and inflammation markers related to EC type 1 progression and patients’ survival data were analyzed.Methods: To measure levels of adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide in 176 preoperative serum samples, the immunoassay technique (EMIT) has been applied.Results: Angiopoietin-2 levels increase with age (P=0.005), FIGO stage (p=0.042), myometrial invasion (P=0.009) and LVSI (P<0.001). The CRP levels increase with age (P=0.01), as well as the advancement of the FIGO stage (P<0.001), higher tumor grade (P=0.012), and myometrial invasion (P<0.001). A positive correlation between serum Ang-2 and CRP levels was demonstrated (r=0.44; p<0.001). Kaplan-Meier survival analysis showed that patients with high CRP levels in serum and Ang-2 presented a worse outcome (P=0.03 and P=0.015, respectively). Cox regression analysis of individual predictors revealed that high serum levels of Ang-2, CRP, advanced clinical FIGO stage (P<0.001, respectively), old age (P=0.013) were all significant overall survival predictors. By means of multivariate analysis, their predictive significance was confirmed.Conclusion: Our study provides evidence that serum levels of Ang-2 and CRP may serve as predictors for assessment of the clinical stage of type 1 EC and are significantly associated with poor prognosis. It is likely that angiogenesis and inflammation associated with obesity have a significant impact on EC type 1 progression and survival rate of patients.

Pre-treatment inflammatory parameters predict survival from endometrial cancer: A prospective database analysis

“…These stimulate the production of CRP, an acute-phase protein that is produced by the liver and released directly into the blood. The potential prognostic utility of CRP has been investigated in many solid malignancies [ 27 ], although endometrial cancer has been relatively understudied [ 16 , 18 , 28 ]. A multicenter study of 403 surgically treated patients found CRP was an independent prognostic marker for endometrioid endometrial cancer [ 16 ].…”

“…CRP was associated with stage, but not tumor grade, LVSI or age at diagnosis [ 16 ], and the study failed to control for other important prognostic parameters, for example BMI, T2DM and depth of myometrial invasion. A small study of 176 women with type 1 endometrial cancer found high pre-operative CRP levels were associated with increased all-cause mortality [ 28 ] but the authors failed to include non-endometrioid tumors in their analysis or adjust for important confounders. Another small study of just 110 women with endometrial cancer demonstrated an association between pre-treatment CRP levels and both overall and disease-free survival [ 18 ].…”

“…CRP is an acute-phase inflammatory protein that correlates with poor outcomes in several adult solid tumors [ 25 , 26 ]. A systematic review found CRP was prognostic in 90% of the 271 included studies [ 27 ], but few assessed its utility in the context of endometrial cancer [ 16 , 18 , 28 ]. Those that did failed to account for important clinical and other prognostic parameters that may explain or confound the association between CRP and survival.…”

Associations of insulin resistance and inflammatory biomarkers with endometrial cancer survival: The Alberta endometrial cancer cohort study

“…To date, only two studies have examined the relationship between insulin resistance and endometrial cancer survival and did not observe associations between presurgical serum concentrations of insulin and recurrence 18 or overall survival. 19 In cohorts of female breast cancer survivors with assessments of biomarkers up to 1 year postsurgery, higher levels of fasting insulin, compared to lower levels, have been associated with increased recurrences, [29][30][31] cancer-specific deaths, 32 and all-cause mortality. 30 Conversely, high versus low levels of fasting glucose have not been associated with recurrence in postmenopausal women previously operate on for breast cancer (HR = 2.42; 95% CI = 0.90-6.53) 29 or with progression-free survival in female breast cancer survivors assessed prior to receiving any treatment (HR = 0.82; 95% CI = 0.44-1.51).…”

“…11,13 Although metabolic dysregulation and chronic inflammation have been linked to the development of endometrial cancer, few studies have examined their impact on endometrial cancer prognosis. [18][19][20][21] In endometrial cancer survivors, obesity has been associated with increased cancer-specific and all-cause mortality 22 whereas, physical activity has been associated with improved diseasefree and overall survival. 23 However, the biological mechanisms underlying these relationships have not been investigated.…”