Bioinformatic Investigation of Genetic Changes in Paraoxonase Genes in Breast Cancer and Breast Cancer Subtypes.

OBJECTIVE: Among women, breast cancer (BC) is the most prevalent form of cancer. Many molecular targets have been discovered for BC prognosis and treatment. However, new markers still need to be identified, as cancer pathogenesis is triggered by different mechanisms. The aim of this study was to examine the changes in the paraoxonase genes (PON1, PON2, and PON 3) involved in the pathogenesis of BC. MATERIALS AND METHODS: The characteristics of the mutations were evaluated with the Cbioportal database. Kaplan-Meier Plot evaluated recurrence-free survival (RFS). The UALCAN database determined the promoter methylation. Gene expression was evaluated by GEPIA2.0 database. RESULTS: PON1 harbored the most mutations. There was a significant decrease in PON3 expression levels in BC samples compared with healthy samples. PON1 and PON2 expression levels did not differ between BC tissue and normal adjacent tissue. Elevated expression levels of PON1 and PON2 genes were correlated with longer RFS, whereas reduced expression of the PON2 gene showed an association with longer RFS. Moreover, the promoter regions of PON1 and PON 3 were found to be hypermethylated, while the promoter region of PON 2 was found to be hypomethylated. The PON3 promoter region was significantly hypermethylated in luminal and human epidermal growth factor receptor 2 (HER2) + BC subtypes. However, the PON3 promoter region was significantly hypomethylated in the triple negative breast cancer (TNBC) subtype. CONCLUSION: These results suggest that methylation and expression status of PON3 in BC and BC subtypes (TNBC, luminal and HER2) may indicate a poor prognosis. The PON3 gene could be a negative prognostic marker in BC. However, the results should be supported by prospective studies.

Can immature granulocytes and neutrophil-lymphocyte ratio be biomarkers to evaluate diabetic nephropathy?: A cross-sectional study.

AIMS: We aimed to examine the role of circulating immature granulocytes (IGs) in assessing Diabetic Nephropathy (DN) mainly and also associations of other leukocyte parameters with DN. METHODS: In this retrospective cross-sectional study, a total of 164 Diabetes Mellitus patients were grouped as normoalbuminuric and microalbuminuric according to urinary albumin excretion in the course of admission. Neutrophil-lymphocyte ratio (NLR), IG count (IG#) and IG percentage (IG%) levels were compared between the groups. The value of IG# and IG% levels in detecting microalbuminuria was analyzed with the Receiver operating characteristic (ROC) curve. RESULTS: NLR was remarkably higher in the microalbuminuric group (p = 0.036). Correlation results in the microalbuminuric group were as follows: A feeble positive correlation between neutrophil count (NEU#) and serum creatinine and albumin-to- creatinine ratio (ACR) (p = 0.036, r = 0.261; p = 0.005, r = 0.347, respectively), a feeble positive correlation between lymphocyte count (LYM#) and estimated glomerular filtration rate (p = 0.021, r = 0.285). Correlation results in the normooalbuminuric group were as follows: A feeble positive correlation between NEU# and ACR (p = 0.043, r = 0.204), a feeble negative correlation between LYM# and serum creatinine (p = 0.042, r = -0.205), a poor positive correlation between IG# and ACR and HBA1C% (p = 0.048, r = 0.199; p = 0.004, r = 0.290, respectively), a positive poor correlation between IG% and HBA1C% (p = 0.019, r = 0.235). Area under the ROC curve values for IG# and IG% were not statistically noteworthy in detecting microalbuminuria (p = 0.430; p = 0.510, respectively). CONCLUSIONS: IG# and IG% values are insufficient to predict immediate microalbuminuria, but could be considered a weak biomarker for renal damage in normoalbuminuric (<30 mg/g) diabetic patients. Further researches are needed for the use of leukocyte parameters in evaluating DN.

Bioinformatic analysis of genetic changes CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3, and NPAS2 proteins in HCC patients.

Background and Aim: Genes related to the circadian rhythm control various biological processes. The aim of this study was to comprehensively investigate the mutational and mRNA profile of core circadian rhythm genes in hepatocellular cancer (HCC) samples. Materials and Methods: In this study, the gene profile of a total of 369 patients with HCC was examined over the data obtained from the cancer genome atlas database through-cBioPortal. The effects of mutations on protein were examined by scoring the Polymorphism Phenotyping v2, Mutation Assessor, and SIFT-databases. While the association of genes with other genes was determined with the GeneMANIA-database, the association of expression levels in the genes with overall survival (OS) was evaluated with the Kaplan-Meier Plot database. Results: As a result of the analyses, there were a total of 25 mutations. Decreased expression levels of PER1 (1.3e-05), PER3 (p=0.046), and CRY2 (p=1.8e-06) genes were found statistically associated with shorter OS. It was also found that increased expression levels of the PER2 (p=0.045) gene were associated with longer OS, and increased expression levels of the NPAS2 (p=9e-04) gene were associated with shorter OS. Conclusion: In particular, changes in the PER1, PER2, CRY2, and NPAS2 genes may provide possible molecular targets in chemotherapy and immunotherapy for HCC patients.

Prevalence of Hemoglobinopathies in Premarital Screening in the Province of Nigde, Turkey.

Hemoglobinopathies are one of the most widespread hereditary disorders in Turkey. The present study aimed to determine the prevalence of hemoglobinopathies in the Nigde province of Turkey. This study was conducted with 2013 individuals who applied for the premarital screening, between January 2019 and December 2021. The complete blood count was measured by an automated hematology analyzer. The types of hemoglobin were determined by high-performance liquid chromatography. A total of 2013 individuals including 951 (47.2%) females and 1062 (52.8%) males, were screened within the premarital screening program, and 67 (3.3%) of them were migrants. 53 out of 2013 (2.63%) individuals were identified as ß thalassemia carriers, and five of them were migrants including two from Afghanistan, two from Iran, and one from Georgia. HbC was observed in two cases, a couple from Syria (0.1%), HbD in two cases (0.1%), HbE in one case from Thailand (0.05%), HbS-ß-thalassemia in one case (0.05%), delta-ß thalassemia in one case (0.05%), and unidentified structural variant in one case (0.05%). Moreover, 183 individuals (9.1%) were considered to have iron deficiency, α-thalassemia, or silent ß-thalassemia carrier. These results indicate that the province of Nigde is a relatively risky region regarding hemoglobinopathies. Geographic location and immigrant population may have slightly affected the local prevalence of hemoglobinopathies and could be taken into consideration to ensure the effective implementation of the hemoglobinopathy prevention program.

Measuring plasma ferritin levels with two different methods: A comparison of Roche Cobas e601 versus Roche Cobas c501 (integrated modular system Roche Cobas 6000).

BACKGROUND: The aim of our study is to compare plasma ferritin levels found to be high or low in terms of reference range by means of electrochemiluminescence (ECLIA) and immunoturbidimetric method and to examine whether they can be used interchangeably. METHODS: 84 patients with high plasma ferritin level and 153 patients with low ferritin level according to the re ference range were included in the study. Plasma samples measured in Cobas e601 device with ECLIA were also measured as immunoturbidimetric Cobas c501 device. For method comparison, CLSI EP9-A3 Guideline was used. While the consistency between the methods were specified with Passing-Bablok regression analysis and Spearman cor relation analysis, bias error between the methods (bias%) was determined through Bland-Altman analysis. RESULTS: Both high and low plasma ferritin levels measured with Cobas e601 module and determined high in terms of reference range were compared with the results found with cobas c501 module. The difference was found to be statistically significant (p<0.001). According to regression and correlation (for low plasma ferritin levels; r: 0.993, p<0.001, for high plasma ferritin levels; r: 0.966, p<0.001) results, the methods were in consistency with each other. Additionally, while the bias% value was found to be 10.4% for low plasma ferritin levels, it was found to be 12.6% for high ferritin levels. CONCLUSIONS: Accordingly, we believe that, comparison with more samples especially in terms of different clinical decision levels is required in order to examine inter changeable use of immunoturbidimetric method in integrated devices and ECLIA.

Evaluation of Paraoxonase, Arylesterase, and Homocysteine Thiolactonase Activities in Patients with Diabetes and Incipient Diabetes Nephropathy.

BACKGROUND: The aim of this study is to examine the relationship among the changes in activities of paraoxonase (PON), arylesterase (ARE) and homocysteine thiolactonase (HTLase) enzyme having antioxidant properties and the development of diabetic nephropathy (DN), one of the most common complications of diabetes. METHODS: Normoalbuminuric type-2 diabetic patients (Group II, n=100), microalbuminuric type 2 diabetic patients (Group III, n=100) and the control group (Group I, n=100) were included in the study. The age and gender of the patient groups matched with the age and gender of the control group. HTLase, PON and ARE enzyme activities were measured by the spectrophotometric method using a g-thiobutyrinolactone, paraoxon, and phenylacetate substrates respectively. In this study, an autoanalyzer application was developed in order to measure HTLase enzyme activity for the first time. RESULTS: Serum HTLase, ARE and PON activities of Group III and Group II were significantly low compared to HTLase, ARE and PON results of Group I (p<0.05). CONCLUSIONS: Based on our results, PON, ARE and HTLase enzyme activities were found to be decreased due to the increase in the degree of DN.

Maternal Serum and Fetal Cord Blood C-Reactive Protein Levels but not Procalcitonin Levels Are Increased in Idiopathic Intrauterine Growth Restriction.

BACKGROUND The aim of the present study was to compare procalcitonin and CRP levels in maternal serum and fetal cord blood samples of patients with idiopathic intrauterine growth restriction (IUGR) vs. a control group of appropriate for gestational age (AGA) infants. MATERIAL AND METHODS The present prospective study included 43 patients: 27 patients with idiopathic IUGR (IUGR group) and 26 AGA infants at similar gestational ages (control group). Maternal serum and fetal cord blood samples were collected from the control group and IUGR group at time of delivery. Procalcitonin and CRP levels were analyzed in maternal blood. Procalcitonin and CRP levels were analyzed in fetal cord blood. RESULTS The median value of CRP levels in maternal blood was 47.5 mg/dl in the IUGR group and 15.255 mg/dl in the AGA group (p=0.001). The mdian CRP level in cord blood was 36.4 mg/dl (range, 17.3-47.2) in the IUGR group and 10.1 mg/dl (range, 4.07-16.5) in the control group, and the difference was statistically significant (p=0.001). The median maternal serum procalcitonin level was 0.05 µg/l in the IUGR group and 0.04 µg/l in the AGA group, and the difference was not statistically significant (p=0.435). The median procalcitonin value in fetal cord blood was 0.06 µg/l in the IUGR group and 0.04 µg/l in the AGA group, and the difference was not statistically significant (p=0.741). CONCLUSIONS Maternal serum and fetal cord CRP levels were higher in the IUGR group; however, there was no difference in procalcitonin, which is another inflammatory indicator, between the groups.

Heterozygous Beta Chain Variant Hemoglobin Pusan: A Rare Case Report in Turkish Population.

The case, detected during routine thalassemia (hemoglobin variant) screening, was a 25-year-old male patient of Turkish origin. Physical examination revealed no abnormal findings. Laboratory findings did not reveal any signs of anemia (iron deficiency, B12 deficiency, etc.). However, when the hemoglobin variant report was being evaluated, it was found that besides the normal hemoglobin peaks, there was another peak that had not been defined before. The sample was sent to genetic analysis for verification with the suspicion of an unknown hemoglobin variant. According to the genetic analysis, the unknown hemoglobin variant was found to be Hemoglobin Pusan (Hb Pusan). The aim of this study is to give information about a hemoglobin variant which is rarely seen in Turkish population and to raise awareness about this hemoglobin variant. In addition, clinical and hematological findings of this disease are discussed in the case report.