Association of Glutathione Peroxidase 3 (GPx3) and miR-196a with Carbohydrate Metabolism Disorders in the Elderly.

The escalating prevalence of carbohydrate metabolism disorders (CMDs) prompts the need for early diagnosis and effective markers for their prediction. Hyperglycemia, the primary indicator of CMDs including prediabetes and type 2 diabetes mellitus (T2DM), leads to overproduction of reactive oxygen species (ROS) and oxidative stress (OxS). This condition, resulting from chronic hyperglycemia and insufficient antioxidant defense, causes damage to biomolecules, triggering diabetes complications. Additionally, aging itself can serve as a source of OxS due to the weakening of antioxidant defense mechanisms. Notably, previous research indicates that miR-196a, by downregulating glutathione peroxidase 3 (GPx3), contributes to insulin resistance (IR). Additionally, a GPx3 decrease is observed in overweight/obese and insulin-resistant individuals and in the elderly population. This study investigates plasma GPx3 levels and miR-196a expression as potential CMD risk indicators. We used ELISA to measure GPx3 and qRT-PCR for miR-196a expression, supplemented by multivariate linear regression and receiver operating characteristic (ROC) analysis. Our findings included a significant GPx3 reduction in the CMD patients (n = 126), especially in the T2DM patients (n = 51), and a decreasing trend in the prediabetes group (n = 37). miR-196a expression, although higher in the CMD and T2DM groups than in the controls, was not statistically significant, potentially due to the small sample size. In the individuals with CMD, GPx3 levels exhibited a negative correlation with the mass of adipose tissue, muscle, and total body water, while miR-196a positively correlated with fat mass. In the CMD group, the analysis revealed a weak negative correlation between glucose and GPx3 levels. ROC analysis indicated a 5.2-fold increased CMD risk with GPx3 below 419.501 ng/mL. Logistic regression suggested that each 100 ng/mL GPx3 increase corresponded to a roughly 20% lower CMD risk (OR = 0.998; 95% CI: 0.996-0.999; p = 0.031). These results support the potential of GPx3 as a biomarker for CMD, particularly in T2DM, and the lack of a significant decline in GPx3 levels in prediabetic individuals suggests that it may not serve reliably as an early indicator of CMDs, warranting further large-scale validation.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer.

Endometriosis-associated ovarian cancer (EOC) consisting of endometrioid cancer and clear-cell ovarian cancer could be promoted by many factors. miRNAs, which are small, non-coding molecules of RNA, are among them. The aim of this study was to detect miRNAs connected with the malignant transformation of endometriosis. FFPE (formalin-fixed, paraffin-embedded) samples of 135 patients operated on for endometriosis and different types of ovarian cancer (EOC and HGSOC-high-grade serous ovarian cancer) were studied. Healthy ovarian tissue was used as a control group. From the expression panel of 754 miRNAs, 7 were chosen for further tests according to their ROC (receiver operating characteristic) curves: miR-1-3p, miR-125b-1-3p, miR-31-3p, miR-200b-3p, miR-502-5p, miR-503-5p and miR-548d-5p. Furthermore, other potentially important clinical data were analysed, which included age, BMI, Ca-125 concentration, miscarriages and deliveries and concomitant diseases such as hypertension, type 2 diabetes and smoking. Among the miRNAs, miR200b-3p had the lowest expression in neoplastic tissues. miR31-3p had the highest expression in women without any lesions in the ovaries. miR-502-5p and miR-548-5p did not differ between the studied groups. The examined miRNA panel generally distinguished significantly normal ovarian tissue and endometriosis, normal ovarian tissue and cancer, and endometriosis and cancer. The malignant transformation of endometriosis is dependent on different factors. miRNA changes are among them. The studied miRNA panel described well the differences between endometriosis and EOC but had no potential to differentiate types of ovarian cancer according to their origin. Therefore, examination of a broader miRNA panel is needed and might prove itself advantageous in clinical practice.

Effective Use of microRNA, BRAF and Sonographic Risk Assessment in Bethesda III Thyroid Nodules Requires a Different Approach to Nodules with Features of Nuclear Atypia and Other Types of Atypia.

The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.

The PD-1 single-nucleotide polymorphism rs11568821 and rs2227981 as a novel prognosis model in a triple-negative breast cancer patient.

INTRODUCTION: The aim of the study is to determine the relationship between polymorphisms rs11568821 C/T and at rs2227981 G/A in the programmed cell death 1 gene (PDCD1) and the clinicopathologic characteristics of triple negative breast cancer patient (TNBC). MATERIAL AND METHODS: The study included 30 TNBC patients and 30 healthy controls. Genotyping was performed with allelic discrimination using PCR with TaqMan SNP Genotyping Assays. RESULTS: The presence of CC/CT in rs11568821and GG/AG in rs2227981 were not associated with the risk of progression of TNBC. The correlation between rs11568821 minor allele distribution and risk of TNBC has borderline significance (p = 0.0619). The rs2227981 polymorphism has a significant association with grade G (G3, p = 0.0229). There was a trend toward significance (p = 0.063448) in the minor allele presentation and Ki67 > 20% for rs2227981. Other clinical features (e.g. age, TNM stage) did not significantly correlate with the rs11568821 or the rs2227981 polymorphism. CONCLUSION: rs2227981 is associated with grading; hence PDCD1 can be used as a prognostic marker in TNBC.

Inflammation-related mRNA expression in patients with multiple myeloma undergoing hematopoietic stem cell mobilization.

Mobilization of CD34+ cells is a key element in the therapy of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation. The use of chemotherapy and the granulocyte colony-stimulating factor can significantly affect the expression of inflammation-related proteins and the migration of hematopoietic stem cells. We assessed the mRNA expression of selected proteins involved in the inflammatory landscape in patients with MM (n = 71). The study aimed to evaluate C-C motif chemokine ligands 3, 4, 5 (CCL3, CCL4, CCL5), leukocyte cell-derived chemotaxin 2 (LECT2), tumor necrosis factor (TNF), and formyl peptide receptor 2 (FPR2) levels in the course of mobilization and their role in the CD34+ collection efficacy. mRNA expression from peripheral blood (PB) plasma was evaluated by Reverse transcription polymerase chain reaction. We observed a deep decline in CCL3, CCL4, LECT2, and TNF mRNA expression on the day of the first apheresis (day A) compared with that at baseline. A negative correlation was observed between CCL3, FPR2, LECT2, TNF level, and the CD34+ cells count in PB on day A, and the number of CD34+ cells obtained at first apheresis. Our results indicate that the investigated mRNAs significantly alter and may regulate the migration of CD34+ cells during mobilization. Moreover, in the case of FPR2 and LECT2, the results obtained in patients differed from the murine models.

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis.

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

Analysis of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in endometrial cancer.

BACKGROUND: The analysis of long non-coding RNA (lncRNA) in endometrial cancer is a novel field of science. Although numerous lncRNA sequences have been identified until today, their correlation with endometrial cancer is still undetermined. The aim of this study was to analyze the expression of four lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 and to investigate their significance in endometrial cancer. METHODS: LncRNA sequences were investigated in paraffin blocks (tumor tissue and non-malignant endometrial tissue in archival postoperative specimens) in endometrial cancer patients (Cases, n = 120) and in cancer-free controls (n = 80) using real-time PCR assay. RESULTS: This study revealed a lower expression of LINC01468 in endometrial cancer patients than in controls. Both LINC01468 and FAM3D-AS1 were positively correlated with Body Mass Index (BMI) in cancer-free controls. CONCLUSIONS: LncRNA LINC01468 may be a protective factor in development of endometrial cancer.

Polymorphism of Interleukin-1 Gene Cluster in Polish Patients with Acute Coronary Syndrome.

BACKGROUND AND OBJECTIVES: Some experimental studies demonstrated adverse modulation of atherothrombosis by interleukin-1beta (IL-1b). To assess the relationship between the five most common variants of three polymorphisms of the IL1b gene cluster and the complexity of coronary atherosclerosis expressed in Gensini Score (GS), and the age of onset of the first acute coronary syndrome (ACS), we assessed the patients (pts) hospitalized due to ACS in this aspect. MATERIALS AND METHODS: 250 individuals were included. The single nucleotide polymorphisms of IL1b gene: transition T/C at -31 position, C/T at -511, and those of IL1 receptor antagonist gene (IL1RN)-variable number of tandem repeats allele 1, 2, 3, or 4-were determined by PCR. GS was calculated from the coronary angiogram performed at the index ACS. The impact of the presence of T or C and allele 1 to 4 at the investigated loci on the mean GS, GS greater than 40, mean age of onset of ACS, and the fraction of pts over 60 years of age at ACS were compared between the five most common genotype variants. RESULTS: The five most common variants were present in 203 pts (81.2%). Patients with pair 22 in ILRN had the lowest rate and those with pair 12 had the highest rate of ACS before 60 years of age (29.4 vs. 67.8%; p = 0.004). GS > 40 entailed an eight-fold increase of risk, as observed when pts with one T allele at locus -31 were compared with carriers of 2 or no T allele at this locus: OR 8.73 [CI95 4.26-70.99] p = 0.04. CONCLUSION: Interleukin-1 beta is subject to frequent genetic variability and our results show a potential relationship of this polymorphism with the extent of coronary atherosclerosis and age at the first ACS.

MiRNA-103/107 in Primary High-Grade Serous Ovarian Cancer and Its Clinical Significance.

High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients' clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer cell lines (A2780, A2780cis, SK-OV-3, OVCAR3). We assessed the relative expression of miRNA-103/107 (quantitative reverse transcription-polymerase chain reaction) in fifty archival formalin-fixed paraffin-embedded tissue samples of primary high grade serous ovarian cancer. Then, miRNA-103/107 and DICER expression levels were evaluated in selected ovarian cancer cell lines. Additionally, DICER, N-/E-cadherin protein levels were assessed with the use of western blot. We identified miRNA-107 up-regulation in ovarian cancer in comparison to healthy tissues (p = 0.0005). In the case of miRNA-103, we did not observe statistically significant differences between cancerous and healthy tissues (p = 0.07). We did not find any correlations between miRNA-103/107 expression levels and clinicopathological features. Kaplan-Meier survival (disease-free and overall survival) analysis revealed that both miRNAs could not be considered as prognostic factors. SK-OV-3 cancer cell lines were characterized by high expression of miRNA-103/107, relatively low expression of DICER (western-blot), and relatively high N-cadherin levels in comparison to other ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study.

The role of childhood adversities, FKBP5, BDNF, NRN1, and generalized self-efficacy in suicide attempts in alcohol-dependent patients.

BACKGROUND: Alcohol-dependent (AD) patients report higher number of adverse childhood experiences (ACEs), develop poor social skills, and have a higher rate of suicide attempts than the general population. We hypothesize that the association between ACEs and lifetime suicide attempts in AD patients is mediated by generalized self-efficacy and selected functional single nucleotide polymorphisms (SNPs) in genes involved in the stress response and neuroplasticity, including: FKBP5 rs1360780, BDNF rs6265, and NRN1 rs1475157. METHODS: 176 AD patients and 127 healthy controls self-reported ACEs with the ACE Study questionnaire and three additional questions that inquired about ACE categories of acute stress; generalized self-efficacy-with the Generalized Self-Efficacy Scale. Genotyping for the three analysed SNPs was performed according to the manufacturer's standard PCR protocol. Hypotheses were tested with bivariate analyses, multiple regression model, and mediation models. RESULTS: Higher levels of generalized self-efficacy were associated with a blunted effect of ACEs on the risk of suicide attempts. The prevalence of the three analyzed SNPs genotypes and alleles did not differ between AD patients with a positive vs. negative lifetime history of suicide attempt and was not associated with GSES scoring. CONCLUSIONS: Generalized self-efficacy should be considered as a target for psychotherapeutic interventions aimed at reducing the risk of suicide attempts in AD patients who were exposed to childhood victimization. The negative results concerning the hypothesized role of the three analysed SNPs should be carefully interpreted due to the relatively small study sample, but represent a theoretical foundation for further research studies with larger study samples.

MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes.

INTRODUCTION: MicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets. MATERIAL AND METHODS: During the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 tissue samples were performed. RESULTS: After the screening phase of the study, five miRNAs were selected (hsa-miR-18b, hsa-miR-148a-5p, hsa-miR-204, hsa-miR-424, hsa-miR-129-1-3p). Validation revealed that miRNA-204 and miRNA-424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa-miR-204-P = .0008; hsa-miR-424-P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa-miR-204-.802 (96% confidence interval CI 0.676-0.927), hsa-miR-424-.84 (95% CI 0.711-0.969). CONCLUSIONS: Compared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA-204 and miRNA-424.

Induction of immediate early genes expression in the mouse striatum following acute administration of synthetic cathinones.

BACKGROUND: Synthetic cathinones (SCs) form one of the most prominent group of the New Psychoactive Substances. SCs enhance central dopaminergic and noradrenergic neurotransmission, and are used as substitutes for illicit psychostimulants, namely cocaine, amphetamine, and methamphetamine. Changes in the expression of immediate early genes (IEGs) in the striatum underlie the addictive potential of drugs of abuse belonging to distinct pharmacologic groups. This work was aimed to assess the impact of acute administration of the prominent SCs on the mRNA levels of IEGs in the mouse striatum. METHODS: Effects of 3,4-MDPV, 2,3-MDPV, α-PVP, PV8, PV9, methcathinone (MC) and 3-fluoromethcathinone (3-FMC) on the mRNA levels of ten IEGs, one and two hours after exposure, were measured in the mouse striatum using the quantitative RT-PCR technique. RESULTS: All SCs used in the study produced increased mRNA levels of the following IEGs: Areg, c-fos, Csrnp1, Dusp1, Dusp14, Egr2, Egr4 and FosB. Additionally, the majority of SCs increased the expression of Homer1 and c-jun. The magnitude of observed changes varied by the drug, analyzed gene and, in many cases, by time after administration. CONCLUSIONS: This study demonstrates that SCs increase the expression of IEGs in the mouse striatum, which may lead to a plethora of effects, as proteins encoded by the analyzed genes are involved in diverse actions, including an acute response to the drug and the neuroplasticity underlying the development of addiction.

NFE2L2 is associated with NQO1 expression and low stage of hepatic fibrosis in patients with chronic hepatitis C.

BACKGROUND: Oxidative stress is extremely important in the pathogenesis of chronic hepatitis C virus (HCV). In response to oxidative stress, adaptive antioxidant defenses are upregulated in the liver. The balance between antioxidant response and oxidative stress plays a key role in hepatic injury in HCV infection. OBJECTIVES: The objective of this study was to assess the hepatic expression of the antioxidant genes GFER (growth factor erv1-like) and NQO1 (NAD(P)H:quinone oxidoreductase-1) and the regulatory gene NFE2L2 (nuclear factor erythroid 2-related factor-2) in liver biopsy specimens obtained from chronic HCV patients with regard to selected clinical parameters and histology, and to determine whether GFER and NQO1 expression is dependent on NFE2L2. MATERIAL AND METHODS: The study group consisted of 42 patients with chronic HCV. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the expression of antioxidant and regulatory genes in liver biopsy samples. RESULTS: Positive correlation was observed between the hepatic expression of NFE2L2 and NQO1 in the chronic HCV patients (p < 0.0001). The hepatic expression of NFE2L2 was significantly lower in patients with advanced liver fibrosis (p = 0.05). However, there was no significant difference in the hepatic expression of GFER and NQO1 in relation to the progression of liver steatosis, inflammation and fibrosis. CONCLUSIONS: The hepatic expression of NFE2L2 is associated with NQO1 and low stage of hepatic fibrosis in patients infected with HCV.

MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients.

INTRODUCTION: TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting MGMT and TP53 functionality. MATERIAL AND METHODS: In 49 GB patients, we analyzed the possible associations between TP53 and its miRNA regulators miR-125b, miR-21, and miR-34a, as well as MGMT and its miRNA regulators miR-181d and miR-648. We evaluated the possible influence of mutational and methylation status on the pre-identified associations. RESULTS: In patients with immunohistochemistry-detected TP53 overexpression, expression levels of miR-34a and TP53 were negatively correlated (r = -0.56, p = 0.0195), and in patients with TP53 mutations, expression levels of TP53 and miR-21 were negatively correlated (r = -0.67, p = 0.0330). In patients with MGMT methylation, expression levels of MGMT were negatively correlated with miR-648 and miR-125b expression levels (r = -0.61, p = 0.0269 and r = -0.34, p = 0.0727, respectively). CONCLUSIONS: Our findings demonstrate that selected miRNAs are significantly correlated with MGMT and TP53 levels, but the extent of this correlation differs regarding the TP53 and MGMT mutational and promoter methylation status.

Serum levels of circulating miRNA-21, miRNA-10b and miRNA-200c in triple-negative breast cancer patients.

INTRODUCTION: Breast cancer can be classified into five subtypes based on variations in the status of three hormonal receptors that are responsible for the cancer's heterogeneity: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These classifications influence the choice of therapies (either neoadjuvant or adjuvant), and the range of prognoses, from good (luminal A subtype) to poor (triple-negative cancers). OBJECTIVE: The aim of the study was to compare the serum concentration of selected miRNAs (miRNA-21, miRNA-10b, and miRNA-200c) between in two groups of breast cancer patients with differing ER, PR, and HER2 statuses. MATERIALS AND METHODS: The study was performed on two groups of patients. One group (TNBC) consisted of patients with triple-negative cancer, and the other group (ER(+)/PR(+)) was comprised of patients with positive ER and PR receptors. RESULTS: The mean level of miRNA-200c was significantly higher in the ER(+)/PR(+) group than in the TNBC group (p < 0.05). No statistically significant difference was found between the two groups with regard to the mean levels of miRNA-21 or miRNA-10b. CONCLUSION: The level of miRNA-200c was lower in triple-negative patients when compared with the levels in the study's ER/PR positive group.

Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer.

PURPOSE: We aimed to compare expression levels of miRNA-21, -103, -129, -150 in primary tumour tissues and its omental metastases from patients operated for advanced ovarian serous cancer. Expression levels of selected miRNAs were correlated with clinicopathological features, including chemosensitivity and survival. METHODS: We performed total RNA extraction from archival formalin-fixed paraffin-embedded tissue samples of primary serous ovarian cancer and omental metastases. The study included 48 patients with advanced ovarian cancer. The reference group consisted of 48 normal ovarian tissue samples. We performed cDNA synthesis, real time polymerase chain reaction and assessed relative expression of selected miRNAs. RESULTS: Samples derived from serous ovarian cancer were characterized by higher expression levels of miRNA-150 in comparison to omental metastases (p = 0.045). Furthermore, we observed that shorter progression free-survival was associated with lower levels of miRNA-150 in metastatic tissues. We did not find similar relationships for other miRNAs. CONCLUSIONS: MiRNA-150 may potentially serve as a prognostic factor in advanced ovarian cancer. However, further studies are required to clearly confirm such hypothesis.

Genetic variants in a Polish population of patients with pulmonary arterial hypertension: sequencing of BMPR2, ALK1, and ENG genes.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a very serious prognosis. It seems that mutations in genes related to transforming growth factor-b signalling pathway are often related to the development of the disease. No study covers this problem in a Polish population. AIM: To screen for genetic mutations in a Polish cohort of patients with pulmonary hypertension, especially with idiopathic PAH, treated in a single hospital in Poland. METHODS: DNA sequencing method was used. Samples from 50 patients with pulmonary hypertension were screened for mutations in type 2 bone morphogenetic protein receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin gene (ENG). RESULTS: No genetic variations were found for the BMPR2 gene. In all 20 samples from idiopathic pulmonary hypertension patients we found heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene. Three samples from these patients showed variations of ENG gene: we found one sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs 3739817, and one with both. CONCLUSIONS: We detected benign polymorphisms or genetic variants of unknown importance. It is possible that the Polish population of PAH patients differs from the previously described populations of other countries in terms of the frequency and importance of mutations in BMPR2, ALK1 and ENG genes.

Association of microRNA-200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer.

INTRODUCTION: MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. MATERIAL AND METHODS: Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. RESULTS: The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. CONCLUSIONS: Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer.

Expression of miR-146a in patients with ovarian cancer and its clinical significance.

The aim of the present retrospective study was to compare microRNA (miR)-146a expression levels in primary tumors and omental metastases of 48 patients, who had undergone surgery for advanced ovarian serous cancer. Possible correlations between miR-146a expression level and clinicopathological features were investigated, including chemosensitivity and survival. miR-146a was evaluated in formalin-fixed, paraffin-embedded samples. miR-146a expression level in primary tumors was demonstrated to be increased in comparison with normal ovary tissues (P=0.02) and metastases (P=0.01). A negative correlation was demonstrated between miR-146a expression in primary tumors and serum levels of cancer antigen 125 (R=-0.37; P=0.03) and Risk of Malignancy Algorithm index (R=-0.79; P=0.0007). Overall survival positively correlated with miR-146a expression in primary tumor tissue samples (R=0.38; P=0.01). Probability of survival was decreased in patients with low miR-146a expression levels in primary tumor tissues (hazard ratio=0.21; P=0.003). Lower levels of miR-146a in primary tumor tissue samples were correlated with a shorter progression-free survival (P=0.04) and platinum-resistance of metastases (P=0.006). In conclusion, miR-146a may be a prognostic marker for serous ovarian cancer.