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.

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).…”

“…Only one study to date has examined the relationship between adipokines (leptin and adiponectin) and endometrial cancer survival and did not observe an association between adiponectin levels and overall survival in women with type 1 endometrial cancer. 19 In breast cancer cohorts, higher levels of adiponectin measured prior to surgery 37 , 38 , 39 and approximately 24 months post‐diagnosis 33 have been associated with better prognosis; however, no associations have been found for leptin. 30 , 37 , 38 , 40 In the current study, higher levels of presurgical adiponectin were associated with improved survival outcomes; however, no associations were found for adiponectin measured postsurgery.…”

“…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 disease‐free and overall survival. 23 However, the biological mechanisms underlying these relationships have not been investigated.…”

Machine Learning-Assisted Ensemble Analysis for the Prediction of Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer

“…Systemic inflammation plays a critical role in promoting the progression and metastasis of many cancers ( 20 – 23 ), and was shown to be associated with the development, progression, and metastasis of cervical cancer ( 24 ). We therefore examined pre-NACT treatment peripheral blood-related inflammatory marker levels in patients with LACC, and the results were consistent with previous findings ( 13 ).…”

Diagnostic and Therapeutic Values of Angiogenic Factors in Endometrial Cancer

“…Terlikowska et al found that in EC type 1 patients, serum Ang-2 levels increased with the depth of myometrial infiltration, lymphovascular infiltration, and age and were highest in patients in FIGO stage III–IV. This suggests a key role of Ang-2 in tumor development and metastasis [ 53 ].…”