Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

Follistatin-like 1 and its paralogs in heart development and cardiovascular disease.

Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels and a leading cause of death worldwide. Thus, there is a need to identify new cardiokines that may protect the heart from damage as reported in GBD 2017 Causes of Death Collaborators (2018) (The Lancet 392:1736-1788). Follistatin-like 1 (FSTL1) is a cardiokine that is highly expressed in the heart and released to the serum after cardiac injury where it is associated with CVD and predicts poor outcome. The action of FSTL1 likely depends not only on the tissue source but also post-translation modifications that are target tissue- and cell-specific. Animal studies examining the effect of FSTL1 in various models of heart disease have exploded over the past 15 years and primarily report a protective effect spanning from inhibiting inflammation via transforming growth factor, preventing remodeling and fibrosis to promoting angiogenesis and hypertrophy. A better understanding of FSTL1 and its homologs is needed to determine whether this protein could be a useful novel biomarker to predict poor outcome and death and whether it has therapeutic potential. The aim of this review is to provide a comprehensive description of the literature for this family of proteins in order to better understand their role in normal physiology and CVD.

Eustress and Distress: Neither Good Nor Bad, but Rather the Same?

The terms "eustress" and "distress" are widely used throughout the scientific literature. As of February 2020, 203 items in the Web of Science show up in a search for "eustress," however, there are almost 16 400 items found in a search for the term "distress." Based on the reasoning in this article, however, it is believed there is no such thing as eustress or distress. The adaptation reaction of an organism under stress is not intrinsically good or bad, and its effect on health or performance depends on a plethora of other interactions of the body with the environment as well as on the history of such interactions. The vagueness of the terms "eustress/distress" has historically led to vast differences in the perception and application of the terms across disciplines. While psychology or sociology perceive eustress as something inextricably linked to positive perception and enhanced cognition, biomedicine perceives eustress as generally associated with better survival, health, or increased longevity, no matter how the event is perceived. In this paper, the authors review the current understanding of the term "eustress" in different fields, discuss possible implications of its misleading use, and suggest that the term may be replaced by "stress" only.

The Pathosome: A Dynamic Three-Dimensional View of Disease-Environment Interaction.

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype-environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype-environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms.

Dietary pattern longitudinality during 8 years in children: results from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ).

OBJECTIVE: Dietary pattern analysis constitutes a suitable method for identifying complex food preferences as well as a useful tool for comparing dietary behaviour across individual populations. In addition to a lack of information on Central European dietary patterns, dietary data featuring a longitudinal aspect are likewise largely unavailable for the region. Our study thus strives to address this gap by analysing children's dietary patterns, their stability and possible changes at 7, 11 and 15 years in the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ). DESIGN: We analysed dietary data based on the self-reported semi-quantitative FFQ obtained in 1998, 2002 and 2006. Dietary patterns were derived using factor analysis for each period, followed by the determination of dietary pattern stability across the individual periods. SETTING: The analysis of dietary patterns was based on longitudinal children's dietary data from the geographical region that was undergoing massive socio-economic changes at the time of birth of the study subjects. PARTICIPANTS: All participants were children. At 7 years the analysis included 3220 children, at 11 years the analysis included 2509 children and at 15 years the analysis included 1589 children. RESULTS: Two stable children's dietary patterns labelled as 'prudent' and 'junk food' were identified across all three time points (7, 11 and 15 years). CONCLUSIONS: This study identifies stable longitudinal trends in the dietary behaviour of children enrolled in the ELSPAC-CZ study.

Assessing Stress in Pregnancy and Postpartum: Comparing Measures.

INTRODUCTION: Measuring early-life psychosocial stress is complicated by methodological challenges. This paper compares three survey instruments for the assessment of life in pregnancy/postpartum and investigates the effects of the timing of early-life stress for emotional/behavioral difficulties (EBD) of offspring during mid/late childhood and adolescence. METHODS: Observational data were obtained from the European Longitudinal Cohort Study of Pregnancy and Childhood (ELSPAC-CZ), which included 4811 pregnancies in two Czech metropolitan areas. We used data collected between 1991 and 2010 at 20 weeks of pregnancy (T1), after delivery (T2), at 6 months postpartum (T3), and at child's age of 7 years (T4), 11 years (T5), 15 years (T6), and 18 years (T7). Life stress was assessed with (1) the Edinburgh Postnatal Depression Scale (EPDS), (2) a stressful life events (SLE) count based on 42-item inventory, and (3) the SLE measure weighted by perceived stressfulness (PS). Each stress measure was administered at T1, T2, and T3. Child's EBD were assessed with the Strengths and Difficulties Questionnaire at T4, T5, T6, and T7. RESULTS: Each stress measure independently predicted long-term EBD. The best data fit was obtained in a model combining EPDS and SLE. Effect sizes for SLEs decreased between the first half of pregnancy and postpartum, while the effect of EPDS increased. DISCUSSION: SLE-based methods capture an aspect of perinatal stress not adequately assessed by EPDS. Combination of psychological distress measures and SLE-based measures is optimal in predicting EBD of the child. Stress measures based on SLE are suitable for early pregnancy, while self-reports of depressive symptoms may perform better in postpartum.

Sibling relatedness rather than father absence predicts earlier age at menarche in ELSPAC cohort.

Many studies during the past 50 years have found an association between father absence and earlier menarche. In connection with these findings, several evolutionary theories assume that father absence is a causal factor accelerating reproductive development. However, a recent study analysing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) found that father absence does not predict age at menarche when adjusted for sibling relatedness. In this study, we have replicated these results in the Czech section of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), which used the same questionnaires as ALSPAC to study a geographically distinct population. Our results support the conclusion that sibling relatedness rather than father absence predicts age at menarche. Furthermore, our results show that age at menarche in 1990s UK and Czech cohorts is very similar despite socioeconomic differences between the two countries.

Correction to: HSPB7 gene polymorphism associated with anthropometric parameters of obesity and fat intake in a Central European population.

We would like to submit the following correction to our recently published paper due to an error in the Table 2. The corrected table is given below.

Association of Glutathione S-Transferase Polymorphisms with Dietary Composition but Not Anthropometry in Obese as Well as Nonobese Individuals.

OBJECTIVES: Glutathione S-transferases (GSTs) are detoxifying enzymes for a number of substrates, including some food compounds. Selected GST polymorphisms have been proven to significantly affect enzymatic activity; however, it is unclear whether this altered metabolism influences dietary composition. The objective of this study was to locate the correlation between GST polymorphisms and selected nutritional parameters, namely, fiber and vitamin C intake. METHODS: This study was conducted on a cohort of 472 individuals (mean age 45.26 years; mean body mass index [BMI] 32.36) from the South Moravian region of the Czech Republic. Basic anthropometrical parameters were measured and no association was found for the selected polymorphisms. Polymorphisms in GSTA1, GSTM1, and GSTT1 were genotyped using a polymerase chain reaction (PCR)-based methodology. Food intake was monitored using a self-administered 7-day questionnaire that was subsequently analyzed with a special focus on vitamin C intake, fiber intake, and total energy intake. RESULTS: For GSTA1 and GSTM1 polymorphisms, an association was observed with fiber intake. Though no association was found with vitamin C intake, mean vitamin C intake was found to be higher than recommended daily values. No association was found with either daily energy intake or anthropometric parameters. CONCLUSION: Based on our results, GST polymorphisms seem to affect dietary composition; however, they have no effect on total energy intake or any association with obesity.

Therapeutic potential of vitamin E and its derivatives in traumatic brain injury-associated dementia.

Traumatic brain injury is one of the most common causes for intervention in neurosurgery. Apart from its acute consequence, it can represent a further burden on individuals as well as society by being associated with significant comorbidity-mainly early-onset dementia. Oxidative stress is one of the crucial mechanisms conferring the damage to nervous tissue, and it is believed it could be, to some extent, influenced by dietary composition, largely by antioxidants contained in the diet. Under stressful conditions, cell-derived reactive oxygen species in the brain can induce the formation of lipid peroxides and the shifting of redox homeostasis. This review discusses the potential of vitamin E as a potent antioxidant and its derived molecules, including vitamin E-based lazaroids, in traumatic brain injury, summarizing the current state of knowledge of its role in TBI-associated dementia.

HSPB7 gene polymorphism associated with anthropometric parameters of obesity and fat intake in a Central European population.

OBJECTIVE: Heat shock proteins act as chaperones at the molecular level and therefore they have been investigated in numerous diseases associated with oxidative stress, including obesity. The aim of this study was to investigate the possible associations of genetic variability in the 3´-untranslated region of the HSPB7 gene (rs1048261) with anthropometric and dietary parameters in a cohort of lean and obese Central European subjects. METHODS: A total of 708 Central European Caucasian individuals were enrolled in this study, 415 obese subjects and 293 non-obese subjects. The rs1048261 genotypes were established using a conventional PCR-based methodology. RESULTS: Significant differences were observed in the total daily fat intake between subjects with AT and TT genotypes (82.6 ± 29.2 g vs. 74.1 ± 31.3 g, p = 0.023) and also borderline significance in daily proportion of fat in the diet between AA and TT genotypes (36.0 ± 4.4% vs. 33.3 ± 5.9%, p = 0.061). Based on the linear regression model we found association between rs1048261 genotype and body fat percentage. CONCLUSIONS: To the best of our knowledge, this is the first study which reports an association of defined genetic variability in the HSPB7 gene, rs1048261, with obesity and its associated anthropometric characteristics and dietary composition.

Vulvar cancer recurrence - an analysis of prognostic factors in tumour-free pathological margins patients group.

OBJECTIVES: To evaluate risk factors associated with the local recurrence of invasive squamous cell vulvar cancer in patient group with tumor-free pathological margins. MATERIAL AND METHODS: This is a retrospective analysis of 47 patients who underwent surgical treatment at University Hospital Brno, the Czech Republic between 2007 and 2014. 24 patients were classified as IB stage and three as II stage. A further 20 patients representing stage III showed the metastatic involvement of regional lymph nodes. Seven prognostic factors were analyzed in relation to local tumour recurrence: tumour size, margin distance, depth of invasion, lymphovascular space involvement (LVSI), midline involvement, metastatic lymph nodes and FIGO stage. RESULTS: All prognostic factors were found to be statistically significant with respect to the risk of local recurrence. The highest risk of local recurrence was observed for the depth of invasion > 5 mm (HR, 12.42 [95% CI; 3.44-44.84]) and for the presence of LVSI (HR, 10.83 [95% CI; 3.87-30.28]). The study also established a clear difference in the risk of local recurrence between patient groups with resection margin < 8 vs. ≥ 8 mm (HR, 4.91 [95% CI; 1.73-13.93; p = 0.003]. CONCLUSIONS: Tumour-free pathological margin of ≥ 8 mm is a major prognostic factor of local recurrence which can be influenced by the surgeon. A perfect knowledge of the extent of the disease prior to surgery supports adequately radical surgical trends. The emphasis is given on adequate radicality as well as on the reduction of overtreatment without worse-ning prognosis by simultaneously preserving the quality of life.

Muscle-specific microRNAs in skeletal muscle development.

Proper muscle function constitutes a precondition for good heath and an active lifestyle during an individual's lifespan and any deviations from normal skeletal muscle development and its functions may lead to numerous health conditions including e.g. myopathies and increased mortality. It is thus not surprising that there is an increasing need for understanding skeletal muscle developmental processes and the associated molecular pathways, especially as such information could find further uses in therapy. The understanding of complex skeletal muscle developmental networks was broadened with the discovery of microRNA (miRNA) molecules. MicroRNAs are evolutionary conserved small non-coding RNAs capable of negatively regulating gene expression on a post-transcriptional level by means of miRNA-mRNA interaction. Several miRNAs expressed exclusively in muscle have been labeled myomiRs. MyomiRs represent an integral part of skeletal muscle development, i.e. playing a significant role during skeletal muscle proliferation, differentiation and regeneration. The purpose of this review is to provide a summary of current knowledge regarding the involvement of myomiRs in the individual phases of myogenesis and other aspects of skeletal muscle biology, along with an up-to-date list of myomiR target genes and their functions in skeletal muscle and miRNA-related therapeutic approaches and future prospects.

Allelic variants in vitamin D receptor gene are associated with adiposity measures in the central-European population.

BACKGROUND: There is an increasing body of evidence suggesting that vitamin D is involved in ethiopathogenesis of obesity and therefore the aim of the study was to investigate whether 5 selected SNPs in VDR (vitamin D receptor) gene are associated also with anthropometry in the obese and non-obese Central-European population. METHODS: A total of 882 Central European Caucasian individuals of Czech origin were recruited (n = 882, 232 M/650 F) and weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold thickness were measured. Univariate and multivariate models were constructed in order to investigate the relationship between anthropometry and VDR polymorphisms. RESULTS: In the univariate modeling, the CC genotype of FokI SNP was associated with reduced waist circumference (ß = -3.48; 95%CI:-7.11;0.15; p = 0.060), sum of skin fold thickness (ß = -6.53, 95% CI: -12.96;-0.11; p = 0.046) as well as total % of body fat (ß = -3.14, 95% CI: -5.18;-1.09; p = 0.003) compared to TT genotype. The AC genotype of ApaI SNP was associated with reduced waist circumference compared to AA genotype (ß = -4.37, 95% CI: -7.54;-1.20; p = 0.007). GG genotype of EcoRV SNP was associated with reduced sum of skin fold thickness compared to AA genotype (ß = -7.77, 95% CI: -14.34;-1.21; p = 0.020). In the multivariate modelling, multiple significant associations of VDR with investigated traits were observed, too. CONCLUSION: Our study suggests that genetic variability in the VDR region may be an important factor influencing anthropometric characteristics associated with obesity.

Keeping up with the Red Queen: the pace of aging as an adaptation.

For decades, a vast majority of biogerontologists assumed that aging is not and cannot be an adaptation. In recent years, however, several authors opposed this predominant view and repeatedly suggested that not only is aging an adaptation but that it is the result of a specific aging program. This issue almost instantaneously became somewhat controversial and many important authors produced substantial works refuting the notion of the aging program. In this article we review the current state of the debate and list the most important arguments proposed by both sides. Furthermore, although classical interpretations of the evolution of aging are in sharp contrast with the idea of programmed aging, we suggest that the truth might in fact very well lie somewhere in between. We also propose our own interpretation which states that although aging is in essence inevitable and results from damage accumulation rather than from a specific program, the actual rate of aging in nature may still be adaptive to some extent.

Modified posterior pelvic exenteration for advanced ovarian malignancies: a single-institution study of 35 cases.

INTRODUCTION: This study aimed to investigate the possible benefits of a complete cytoreduction in patients with advanced ovarian cancer and concomitant rectal invasion. Furthermore, we evaluated the morbidity associated with radical surgery. MATERIAL AND METHODS: A retrospective analysis examined 35 women who underwent radical surgery in the form of modified posterior pelvic exenteration. Descriptive statistics, Kaplan-Meier survival curves and log-rank test were used for statistical estimations. Surgical complications were analyzed using the Clavien-Dindo classification. RESULTS: The analysis of survival in relation to residual disease assessed according to Sugarbaker confirmed an optimistic prognosis in patients with optimal debulking with a mean disease-free survival period of 33.6 months in R0 patients, 19.6 months in R1 patients, and 14.3 months in R2 patients. A statistically significant difference in disease-free survival (p = 0.023) was observed between the R0 (without residual disease) and R1+2 (with residual disease) groups. Surgical complications occurred in 83% of patients, with early postoperative complications being most frequent (65.7%). While grade III-IV complications occurred in 37.7% of all patients, no cases of surgery-associated mortality occurred. CONCLUSIONS: Modified posterior pelvic exenteration is a highly effective method for achieving optimal debulking in cases of advanced ovarian cancer with the direct invasion of the rectum. Modified posterior pelvic exenteration does not delay the beginning of complementary chemotherapy. However, it is necessary to take into account surgery-related morbidity. As modified posterior pelvic exenteration represents an extremely invasive technique, the surgical plan and perioperative care should be personalized to address the individual medical and surgical conditions of each patient.

Higher Energy Intake Variability as Predisposition to Obesity: Novel Approach Using Interquartile Range.

OBJECTIVE: It is known that total energy intake and its distribution during the day influences human anthropometric characteristics. However, possible association between variability in total energy intake and obesity has thus far remained unexamined. This study was designed to establish the influence of energy intake variability of each daily meal on the anthropometric characteristics of obesity. METHODS: A total of 521 individuals of Czech Caucasian origin aged 16­73 years (390 women and 131 men) were included in the study, 7-day food records were completed by all study subjects and selected anthropometric characteristics were measured. The interquartile range (IQR) of energy intake was assessed individually for each meal of the day (as a marker of energy intake variability) and subsequently correlated with body mass index (BMI), body fat percentage (%BF), waist-hip ratio (WHR), and waist circumference (cW). RESULTS: Four distinct models were created using multiple logistic regression analysis and backward stepwise logistic regression. The most precise results, based on the area under the curve (AUC), were observed in case of the %BF model (AUC=0.895) and cW model (AUC=0.839). According to the %BF model, age (p<0.001) and IQR-lunch (p<0.05) seem to play an important prediction role for obesity. Likewise, according to the cW model, age (p<0.001), IQR-breakfast (p<0.05) and IQR-dinner (p <0.05) predispose patients to the development of obesity. The results of our study show that higher variability in the energy intake of key daily meals may increase the likelihood of obesity development. CONCLUSIONS: Based on the obtained results, it is necessary to emphasize the regularity in meals intake for maintaining proper body composition.

Pre-treatment VD levels and VDR receptors as potential predictors of occurrence and overall survival in paediatric patients with solid tumours-a single institution pilot study.

Recently, vitamin D has been recognized as an important player in the immune system, and multiple studies suggested its involvement in cancer, too. The aims of this study were to investigate selected single nucleotide polymorphisms (SNPs) in the VDR gene, BsmI (rs1544410; A > G), FokI (rs 2228570; C > T), TaqI (rs731236; T > C), ApaI (rs 7975232; C > T) and Cdx-2 (rs11568820; A > G), and to evaluate their possible predictive role for outcomes in patients with paediatric solid tumours. A total of 111 children with paediatric solid tumours were enrolled at the Department of Paediatric Oncology, University Hospital Brno (Brno, Czech Republic) along with a control population of 787 adults; all study subjects were available for genotyping of selected SNPs, and the prediagnostic levels of 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in the cases, too. In FokI, the heterozygote CT genotype was weakly associated with a decreased risk of paediatric solid cancer occurrence 0.82 (0.53-1.28), while the CC genotype was associated with a decreased risk of 0.58 (0.30-1.09), p = 0.09. The 1,25(OH)2D3 prediagnostic levels were indicative of the overall survival in the cases (ß = -0.012, HR 0.988, 95 % CI (0.978-0.998), while higher prediagnostic levels of 1,25(OH)2D3 were associated with a statistically significant increase in overall mortality. We observed multiple effects of the alleles of the investigated polymorphisms and of 1,25(OH)2D3 on overall survival, regardless of the underlying disease.

The common polymorphism Val109Asp in the omentin gene is associated with daily energy intake in the Central-European population.

BACKGROUND: Omentin is an adipokine expressed predominantly in visceral adipose tissue, with adipose tissue stromal cells being the main source. Very little is known about the relationship between the genetic variability of the omentin gene and pathophysiology of obesity, although omentin is believed to play an important role in visceral obesity development. The aim of the study was to investigate two common polymorphisms in the omentin gene (rs2274908 and rs2274907) and dietary composition and anthropometric parameters of obesity in the Central European population. MATERIAL AND METHODS: A total of 495 subjects were included into the study, they were further dividend into the non-obese, obese, and morbidly obese cohorts. Dietary habits were established using the 7-day food records and selected anthropometric parameters were measured. RESULTS: There were significant differences in genotype distributions of rs2274907 between the obese and morbidly obese cohorts (P = 0.01). In the multivariate modelling, the rs2274907 polymorphism expressed independent prediction role for the daily energy intake, independently on the age and gender (P = 0.03); the TT genotype associated with the lowest (7877 ± 2780 J/day) and the AA genotype with the highest (8764 ± 2467 J/day) average energy intake. The rs2274907 also significantly associated with the daily consumption of fat and proteins. CONCLUSION: This is, so far, the first study to investigate the polymorphisms in the omentin gene in a large population cohort of obese and non-obese individuals. Based on our results, the rs2274907 polymorphism is associated with the daily energy intake as well as daily intake of fat and protein.

Prognostic value of human epididymis protein 4 in endometrial cancer and its utility for surgical staging.

AIM: An optimal surgical staging in the group of patients with the high-risk type of endometrial cancer is often limited by age and serious internal comorbidities. Therefore, in this study we focused on human epididymis protein 4 and its contribution to the preoperative differentiation of prognostically distinct groups of patients and to individualized surgical treatment as compared with cancer antigen (CA) 125 and imaging methods. MATERIAL AND METHODS: The study included 115 patients with endometrioid adenocarcinoma diagnosed through endometrial biopsy. Before the final operation, blood sampling was performed for the determination of human epididymis protein 4 (HE4) and CA125 levels. Serum levels of both biomarkers were analyzed in relation to individual prognostic factors (stage of disease, depth of myometrial invasion, tumor grade, risk type of disease). RESULTS: In the case of HE4, we demonstrated a statistically significant difference (P < 0.001) between patients with low and high risk of the disease. In our model, achieving the maximum sum of sensitivity and specificity, HE4 shows a sensitivity of 72.4% and a specificity of 75.4% for the cut-off 76.5 pmol/L and is a better predictor in distinguishing the high-risk patients than CA125 (area under the curve 0.77 for HE vs 0.71 for CA125). CONCLUSION: HE4 is a marker that could complement the findings of imaging techniques and that may be useful in decision-making on how to individualize surgical staging. The possibility of its introduction as an independent marker in routine practice remains, at the moment however, limited. The optimal cut-off for HE4 has not been established yet and further studies are needed.