Matrix Metalloproteinase-2 Promoter Genotype as a Marker of Cutaneous T-Cell Lymphoma Early Stage

The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (−1575G/A, −1306C/T, and −790T/G) were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.). To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages

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 worse­ning prognosis by simultaneously preserving the quality of life

Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature

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.ISSN:0265-9247ISSN:1521-187

Association of Picky Eating with Weight and Height—The European Longitudinal Study of Pregnancy and Childhood (ELSPAC–CZ)

Objective: This study aimed to evaluate whether preschool children identified as picky eaters showed differences in anthropometric characteristics (weight and height) from their non-picky peers at 15 years of age. Design: This study was performed among the cohort members of the EL- SPAC–CZ study, a longitudinal study of pregnancy and childhood. The analysis included 2068 children (997 girls and 1071 boys) followed between births and 15 years of age. Picky eaters were identified at 1.5, 3, and 5 years of age. Anthropometric characteristics were measured at 15 years of age (15 years). Results: Picky eaters (n = 346; 16.7%) had a lower weight and height than non-picky eaters (n = 1722; 83.3%) at 15 years. This difference in weight and height was maintained after controlling for sex of the child, birth weight, birth length, maternal education, family structure at 15 years, and maternal age at childbirth. The picky children were on average 2.3 kg lighter and 0.8 cm shorter than non- picky children at 15 years. Conclusions: Persistent picky eating in preschool children is related to lower weight and height at 15 years of age in ELSPAC–CZ study

Irisin Maternal Plasma and Cord Blood Levels in Mothers with Spontaneous Preterm and Term Delivery

Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB) by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661). Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p=0.046). On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence

B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF’s proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia

Common polymorphisms in <it>GSTM1, GSTT1, GSTP1, GSTA1</it> and susceptibility to colorectal cancer in the Central European population

Abstract Background Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics. Methods In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. Results None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043). Conclusions The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.</p