Gene Expression Levels In Patients Research Articles

Type III Collagen RNA Level Expression in Pelvic Organ Prolapse: A Systematic Review and Meta-Analysis.

Changes in the expression of type III collagen have been linked to women's predisposition to pelvic organ prolapse (POP); however, the findings of prior studies have been conflicting. This study was aimed at investigating whether changes in the type III collagen gene expression levels occur in POP development. A systematic review and meta-analysis were conducted on research articles that evaluated type III collagen gene expression levels in patients with POP compared with those without the condition. The articles, published between January 2000 and February 2024, were obtained from PubMed, ScienceDirect, Semantic Scholar, and EBSCO databases. Data were analyzed using fixed-effect models, and the pooled standardized mean difference (SMD) was calculated. Cochrane's Review Manager 5.4 was used for the analysis. The aggregated SMD with 95% confidence interval (CI) regarding type III collagen gene expression levels relative to POP development was the main outcome measure. Results with p < 0.05 were considered statistically significant. Six studies were included in our analysis, comprising 229 POP cases and 139 non-POP cases. Our meta-analysis indicated that patients with POP had higher type III collagen gene expression levels than those without POP (SMD = 0.32; 95% CI: 0.07 to 0.56; p = 0.01). The results of this study provide evidence that a higher type III collagen gene expression levels is significantly associated with POP.

Prognostic value of the BAP1 gene expression level in patients with clear cell renal cell carcinoma

Prognostic value of the BAP1 gene expression level in patients with clear cell renal cell carcinoma

Estimation of BMP-15 gene expression and its Association to Hormonal Profile in Iraq Patient with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive aged women. The objective of this study was determine the gene expression levels in patients with PCOS and its reflects in hormonal reproductive : Luteinizing hormone(LH), Prolactin hormone(PRL) , Testosterone hormone (T), Follicle Stimulating hormone (FHS) , estradiol (E2). Fifty patient with PCOS and twenty healthy control group recruited from the Al-Zahra Teaching Hospital and AL-karama Teaching Hospital, in Wasit provinces/Iraq ,based on criteria of Rotterdam.The hormonal profile was carried out by Addendum-Mini VIDAS apparatus. BMP-15 gene expression was estimated by quantitative real-time polymerase chain reaction (qRT-PCR). The mean of Testosterone(1.58±0.17), prolactin (18.42± 1.12), Luteinizing hormone (10.98 ± 0.89 ) was a significant (P&lt;0.05) and follicle-stimulating hormone (8.35± 0.42) was high significant (P≤0.01) but the Estradiol hormone decrease in patient with PCOS (39.73± 2.76) was a significant (P&lt;0.05) when compared to healthy control group (0.412±0.04),(13.12±1.13), (5.06±0.40), (6.83±0.34), (49.73±3.43) respectively. The result of BMP-15 gene expression in patient with PCOS that were a significant (P&lt;0.05) . The result showed there were non-significant correlation between PMP-15gene expression and hormonal profile of (E2, PRL,FSH, LH and T). The women with PCOS have high levels of the hormone (LH, PRL, T and FSH) and low levels of the E2 hormone and the gene expression of BMP-15 was high level in patient with PCOS.

Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Prognostic Value of IGF2BP3 Gene Expression Levels in Patients with Acute Myeloid Leukemia

To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML). High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis. In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016). The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Abstract 5183: Retrospective analysis of CCNG1 expression in tumors, a novel biomarker in development for partnering with DRG-101, a tumor targeted retrovector encoding a CCNG1 inhibitor gene

Abstract Background: CCNG1, a non-canonical cyclin, is a novel biomarker in development for partnering with DRG-101 (DeltaRex-G), a tumor targeted retrovector encoding a CCNG1 inhibitor gene. Expanded access using DRG-101 is currently open for an intermediate-size population of advanced pancreatic cancer, sarcoma and carcinoma of breast (NCT04091295). Therefore, it is important to identify patients who might respond favorably to DRG-101 gene therapy. Previously, we reported that CCNG1 expression is enhanced in sarcoma tumors (Ann Oncol 34, 1980P, 2023). In this report, we have expanded the analysis to 137 patients with all cancer types and describe patients with known CCNG1 expression levels who have been treated with DRG-101. Methods: Archived formalin-fixed paraffin-embedded (FFPE) tumor specimens (n=137) from patients who were followed at the Sarcoma Oncology Research Center were collected, processed, and subjected to RNA sequencing. Briefly, RNA-seq libraries were sequenced to generate 50 million reads, aligned using Kallisto v0.42.4 to GENCODE v23 transcripts with default parameters. Only protein-coding, IGH/K/L- and TCR-related transcripts were retained for downstream processing, resulting in 20,062 protein-coding genes. Gene expression levels in patients of the reference cohorts are categorized as low/medium/high, defined by Low = &amp;lt; 17%; Medium-high = 50%-83%; Medium-low = 17%-49%; High = &amp;gt;83%. Results: Seventy women and sixty-seven men, ranging in age from 16 to 87 years, were studied. All tumors showed enhanced CCNG1 expression. Thirty (22%) tumors exhibited high CCNG1 expression, 53 (39%) showed medium-high CCNG1 expression, 48 (35%) displayed medium-low CCNG1 expression, and six (4%) had low CCNG1 expression. One hundred (73%) patients had metastatic disease, and 37 (27%) had localized disease. There was no correlation between CCNG1 expression and disease stage. As a result of these findings, the FDA-CBER authorized the use of DRG-101 in an Expanded Access program as platform therapy upon which one or more FDA approved cancer drugs/immunotherapies may be added. Historically, one patient with metastatic pancreatic cancer, one with early stage, HR+ HER2+ invasive breast cancer and one with early stage triple negative breast cancer are alive 15, 3 and 2.5 years in sustained remission with DRG-101 therapy, and had 24%, 23% and 74% CCNG1 tumor expression levels respectively. Five patients with advanced pancreatic cancer, sarcoma and breast cancer and known CCNG1 expression levels are currently being treated with DRG-101. Conclusions:(1) 100% of tumors tested showed enhanced CCNG1 expression at varying levels, and (2) the use of DRG-101 in combination with FDA approved cancer drugs/immunotherapies is on-going for an intermediate size population of advanced pancreatic cancer, sarcoma and carcinoma of breast. Citation Format: Nadezhda Omelchenko, Vaishali Kumar, Samantha Jeffrey, Grace Haroun, Don Brigham, William H. Isacoff, Sant Chawla. Retrospective analysis of CCNG1 expression in tumors, a novel biomarker in development for partnering with DRG-101, a tumor targeted retrovector encoding a CCNG1 inhibitor gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5183.

Prognostic model of hepatocellular carcinoma based on cancer grade.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. With highly invasive biological characteristics and a lack of obvious clinical manifestations, HCC usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary HCC are still unclear. To select the characteristic genes that are significantly associated with the prognosis of HCC patients and construct a prognosis model of this malignancy. By comparing the gene expression levels of patients with different cancer grades of HCC, we screened out differentially expressed genes associated with tumour grade. By protein-protein interaction (PPI) network analysis, we obtained the top 2 PPI networks and hub genes from these differentially expressed genes. By using least absolute shrinkage and selection operator Cox regression, 13 prognostic genes were selected for feature extraction, and a prognostic risk model of HCC was established. The model had significant prognostic ability in HCC. We also analysed the biological functions of these prognostic genes. By comparing the gene profiles of patients with different stages of HCC, We have constructed a prognosis model consisting of 13 genes that have important prognostic value. This model has good application value and can be explained clinically.

Investigation of &lt;i&gt;PTEN&lt;/i&gt; Gene Expression Levels in Patients with Different Stages and Grades of Breast Cancer

Investigation of &lt;i&gt;PTEN&lt;/i&gt; Gene Expression Levels in Patients with Different Stages and Grades of Breast Cancer

Immune-Related Gene Profile in HIV-Infected Patients with Discordant Immune Response.

In spite of many reports on persistent low CD4 T cell counts and change in immune-related gene expression level in patients with HIV infection, there is still uncertainty about significant association between gene expression level and HIV infection in patients with and without DIR. The aim of this study was to compare the expression level of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes in HIV-1-positive patients with and without DIR. In this study, 30 HIV-1-positive patients (15 patients with and 15 patients without DIR [control group]) were included. PBMCs of the patients were collected through density radient centrifugation with Ficoll-Hypaque. RNeasy Plus Mini kit was used to extract RNA. Relative expression levels of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes were evaluated by real-time PCR. The data were analyzed using one-way ANOVA. CD4 T cell counts were significantly lower in DIR patients than the control group (p < 0.01). While there was no significant difference in the relative expression levels of CD4, CCL5, IFN-γ, STAT1, CD45, and ICAM-1 between patients with DIR and control group, APOBEC3G expression level was significantly higher in the patients with DIR as compare to the control group (p < 0.01). Our findings suggest a significantly higher APOBEC3G expression level in patients with DIR, suggesting the potential role of APOBEC3G in patients with immunological discordance besides its suppressing role in HIV-1 infection. Confirmation of this hypothesis requires further research.

Upregulation of KAT2B and ESCO2 gene expression level in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition that causes progressive inflammation. It seems that alternations in epigenetic modifications contribute to RA development. The present study aimed to assess the expression pattern of K (lysine) acetyltransferase 1 (KAT1; HAT1) and lysine acetyltransferase 2B (KAT2B; PCAF), and the establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) in peripheral blood mononuclear cells (PBMCs) from RA patients. In this case-control study, we studied 50 cases with RA in comparison to 50 age- and gender-matched healthy subjects. Separation of PBMCs samples from whole blood, extraction of RNA, and reverse transcription were performed. Gene transcript levels of KAT1, KAT2B, and ESCO2 were determined using SYBR green real-time quantitative PCR. Our results exhibited a significant upregulation in the expression levels of ESCO2 and KAT2B genes in patients with RA compared to normal individuals (P-value < 0.0001). Similarly, we observed higher expression of KAT1 in the patients' group when compared to the healthy controls, although the difference in expression level failed to show any significant changes (P-value = 0.485). Also, we found a positive correlation between ESCO2 and the level of erythrocyte sedimentation rate (ESR) in patients. Collectively, our results suggest that upregulated expression of KAT2B and ESCO2 genes may be correlated to RA development. Further studies with largersample sizes are required for understanding the potential contribution of these enzymes in the pathology of RA. Key Points • Dysregulated expression level of epigenetics enzymes was observed in PBMCs from RA patients. • The expression of KAT2B was 2.44 times higher in the PBMCs of RA patients than in the healthy subjects. • The expression of ESCO2 was upregulated (2.75 times) in the PBMCs of RA patients compared to the control group. • There was a positive correlation between ESCO2 expression and the ESR level in patients.

Prognostic Significance of CCNB2 Expression in Triple-Negative Breast Cancer.

PurposeThe aim of this study was to explore potential gene therapy targets for triple-negative breast cancer (TNBC).Patients and MethodsThree gene expression profiles (GSE64790, GSE62931, and GSE38959) from the Gene Expression Omnibus (GEO) database were analyzed. The GEO2R analysis tool was used to screen for differentially expressed genes (DEGs) between TNBC and normal tissues, followed by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs. The protein–protein interaction network of DEGs was visualized using Metascape to identify the core genes. Subsequently, transcriptional data for the core genes in patients with breast cancer were investigated in the ONCOMINE database. Kaplan–Meier survival analysis was used to evaluate the prognostic value of core gene expression levels in patients with TNBC. Finally, the clinicopathological and long-term follow-up data of 39 patients with TNBC were retrospectively analyzed at the First Affiliated Hospital of the Bengbu Medical College between January 2014 and July 2020. Immunohistochemistry was used to evaluate the expression and subcellular localization of CCNB2 in TNBC tissues.ResultsA total of 66 DEGs were identified between TNBC and normal tissues, including 33 upregulated and 33 downregulated genes in TNBC. Furthermore, a potential protein complex was identified for five core genes. The high expression of these core genes, especially the overexpression of CCNB2, was correlated with a poor prognosis of patients with TNBC. The CCNB2 protein was expressed in the cytoplasm, and its expression was significantly higher in TNBC tissues than that in the adjacent nontumor tissues. Overall survival of patients was significantly correlated with the expression of CCNB2 (p < 0.05).ConclusionCCNB2 may play a crucial role in the development of TNBC and has the potential to be used as a prognostic biomarker for TNBC.

FOXP3 and IL-10 overexpression: A novel diagnostic biomarker in Iraqi patients having hyperthyroidism treated with radioactive iodine

BackgroundThyroid gland diseases are public health problem worldwide. Further studies are still needed to investigate novel markers for prognosis of thyroid glands after internal radiation exposure. MethodologyqPCR was used to quantitatively determine the expression of FOXP3 and IL-10 transcripts in human whole blood samples of hyperthyroidism and normal health control individuals. ResultsLow level of FOXP3 gene expression (P < 0.01) observed in blood samples of Graves' disease and toxic multinodular goiter patients in comparison to the normal healthy control individuals. Results showed that FOXP3 gene expression increased significantly (P < 0.01) after one and four months of treatment with two doses of RAI-131 (10 and 20 mCi respectively). In contrast, high expression of IL-10 observed in Graves' disease patients, it increased significantly (P < 0.01) after one month of treatment, while it decreased significantly after four months of treatment. There was a significant correlation (P < 0.01) between FOXP3 and IL-10 gene expression before and after one month of treatment with RAI-131 (r = 0.152, and 0.446, respectively). ConclusionFOXP3 and IL-10 gene expression levels in patients having Hyperthyroidism might be effective diagnostic biomarker. The increase in IL-10 and FOXP3 after radiotherapy enhances immunological response of T cell and immune system. It optimizes the opportunity of detection and remission of autoimmune thyroid disease.

Prognostic Implications of Immune-Related Gene Pairs Signatures in Bladder Cancer.

Compelling evidence indicates that immune function is correlated with the prognosis of bladder cancer (BC). Here, we aimed to develop a clinically translatable immune-related gene pairs (IRGPs) prognostic signature to estimate the overall survival (OS) of bladder cancer. From the 251 prognostic-related IRGPs, 37 prognostic-related IRGPs were identified using LASSO regression. We identified IRGPs with the potential to be prognostic markers. The established risk scores divided BC patients into high and low risk score groups, and the survival analysis showed that risk score was related to OS in the TCGA-training set (p < 0.001; HR = 7.5 [5.3, 10]). ROC curve analysis showed that the AUC for the 1-year, 3-year, and 5-year follow-up was 0.820, 0.883, and 0.879, respectively. The model was verified in the TCGA-testing set and external dataset GSE13507. Multivariate analysis showed that risk score was an independent prognostic predictor in patients with BC. In addition, significant differences were found in gene mutations, copy number variations, and gene expression levels in patients with BC between the high and low risk score groups. Gene set enrichment analysis showed that, in the high-risk score group, multiple immune-related pathways were inhibited, and multiple mesenchymal phenotype-related pathways were activated. Immune infiltration analysis revealed that immune cells associated with poor prognosis of BC were upregulated in the high-risk score group, whereas immune cells associated with a better prognosis of BC were downregulated in the high-risk score group. Other immunoregulatory genes were also differentially expressed between high and low risk score groups. A 37 IRGPs-based risk score signature is presented in this study. This signature can efficiently classify BC patients into high and low risk score groups. This signature can be exploited to select high-risk BC patients for more targeted treatment.

Investigation of the miRNA146a and miRNA155 gene expression levels in patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease and the most common neurodegenerative status. MicroRNAs play an important role in macrophage response to inflammatory processes, and alterations in miRNA levels trigger the inactivation of specific T lymphocytes. As a result, these factors can lead to autoimmune diseases such as MS. Therefore, to determine the role of MicroRNA-146a and MicroRNA-155 in MS patients, their expression levels in serum of MS patients were compared with healthy controls.In this study, the expression levels of MicroRNA-146a and MicroRNA-155 in 30 serum samples of MS and healthy patients as a control group. MicroRNA extraction and cDNA synthesis was performed according manufacture protocols. The expression levels of MicroRNAs were evaluated by Real Time-PCR.MicroRNA-146a and MicroRNA-155 levels were increased in patients with MS compared to controls. The results demonstrated that EDSS score are increased with increasing level of MicroRNA-146a and MicroRNA-155. ROC curve analysis showed that the area under curve (AUC) was significant for MicroRNA-146a and MicroRNA-155.Increased expression levels of MicroRNA-146a and MicroRNA-155 may be associated with the pathogenesis of MS disease. If this study is conducted in a larger sample population and the above results can be used to identify patients or control patients who are under medical care.

The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: A randomized controlled trial.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory disease that affects the joints and consequently leads to the destruction of cartilage and bone lesions. Traditionally, ginger has been consumed in treatment of osteoarthritis, joint and muscle pain, neurological diseases, and inflammation of gums, tooth pain, asthma, stroke, diabetes, and constipation. The aim of this study was to determine the effect of ginger on some immunological and inflammatory markers in patients with rheumatoid arthritis. Methods: In this study, which was performed during 2013-2016, 66 patients with active rheumatoid arthritis who referred to the rheumatology clinic at Shariati hospital were en-rolled. Patients were randomly divided into 2 groups: one group consumed 1.5 gr ginger per day, and the other group took roasted wheat flour (placebo), respectively. To determine the effect of confounding factors on the findings of the study, questionnaires for nutrient intake, physical activity, and medication were filled, and BMI was measured. For each participant, at the beginning and end of the study, Serum hs-CRP and mRNA levels of IL-1β, IL-2 and TNF-α were determined by ELISA and Quantitative Real Time PCR, respectively. Statistical analysis was performed using SPSS software. Significance level was set at p<0.05. Results: Results of the study showed ginger powder supplementation caused a significant decline in CRP (p=0.050) and IL-1β mRNA level (p=0.021). TNFα mRNA levels reduced in ginger group compared to placebo groupalthough the difference was not significant between the 2 groups (p=0.093). Ginger had no effects on IL2 gene expression. Conclusion: This study showed that ginger reduces inflammatory factors hs-CRP and IL-1β gene expression in patients with active RA and it seems that ginger can improve the inflam-mation in the patients.

The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: A randomized controlled trial

The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: A randomized controlled trial

FBN-1, FN-1 and TIMP-3 gene expression levels in patients with thoracic aortic aneurysm

Abstract Background Aortic aneurysm occurs in the thoracic and abdominal sections of the aorta and is a deadly late-age-at-onset disease. Thoracic aortic aneurysms (TTAs) are characterized by progressive smooth muscle cell rarefaction due to impaired extracellular matrix. The aim of this study was to investigate fibrillin-1 (FBN-1), fibronectin-1 (FN-1) and tissue inhibitors of metalloproteinases-3 (TIMP-3) gene expression levels in patients with TTA. Materials and methods The data were analyzed for 16 patients treated for TAA and nine control subjects. Tissue samples obtained during surgery were frozen immediately in liquid nitrogen and stored at −80°C until RNA isolation. Gene expression analysis was performed by quantitative reverse transcription polymerase chain reaction for each gene and Beta actin was used as control gene. 2−ΔΔCT method was used for the determining expression levels of the genes. Results According to the results of this study, TIMP-3 gene was nine-fold higher expressed in TAA tissues (p = 0.034). Furthermore, TIMP-3 expression levels were found associated with fasting blood glucose, red blood cells and ejection fraction. The gene expression levels of FBN-1 and FN-1 were not statistically significant (p &gt; 0.05). Conclusion In this clinical trial, we concluded that TIMP-3 expression increases in dilated aorta.

Change of ROCK1 Gene Expression Level in Patients with Acute Lymphoblastic Leukemia and Its Clinical Significance

To investigate the expression change of ROCK1 gene in patients with acute lymphoblastic leukemia (ALL) and its prognostic significance. Sixty patients with ALL were selected in our hospital from April 2017 to April 2018, and 60 healthy persons subjected to physical examination were selected as control. The venous blood was taken from the subjects, and then the mononuclear cells were separated. The ROCK1 gene expression level in the samples was detected by RT-PCR, and the expression level of ROCK1 protein was detected by Western blot. The correlation between ROCK1 gene expression and clinical characteristics of ALL patients was analyzed by using statistical methots. The RT-PCR showed that the relative expression level of ROCK1 gene in ALL patients was 1.37 (1.28-1.46), which was significantly higher than that in the control group (P<0.05). Western blot showed that the protein expression level of ROCK1 in ALL patients was higher than that in the control group (P<0.05). The expression level of ROCK1 gene correlated with age, WBC count, lactate dehydrogenase (LDH) level, peripheral blood immature cell count, and risk stratification of ALL patients (P<0.05). The expression level of ROCK1 gene did not correlate with sex, hemoglobin (Hb) level, platelet count and immunophenotype in ALL patients (P>0.05). The standard risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly higher than that in patients with high ROCK1 expression (P<0.05). The high risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly lower than those with high ROCK1 expression (P<0.05). The ratio of CR in the group with low ROCK1 expression patients was significantly higher than that in patients with high ROCK1 expression (P<0.05). The Relapse rate of the group with low ROCK1 expression was significantly lower than that of the group with high ROCK1 expression (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in ALL patients with low ROCK1 expression were superior to those in ALL patients with high ROCK1 expression (P<0.05). Multiple factor Cox regression analysis showed that age and ROCK1 gene were independent influencing factors for OS (P<0.05); leukocyte count and ROCK1 gene were independent influencing factors for DFS (P<0.05). The expression level of ROCK1 gene in ALL patients is high, which may stimulate the genesis of ALL, and the down-regulation of ROCK1 gene expression may help improve the therapeutic effect for ALL patients.

On the Links between Arterial and Venous Thrombosis: A Comparative Genomic Analysis of Cardiovascular Disease and Venous Thromboembolism

Background: The formation of thrombi inside arteries and veins is a process that underlies the pathogenesis of the most important causes of morbidity and mortality in the modern world: namely cardiovascular diseases (CVD), a term encompassing acute myocardial infarction (AMI), ischemic stroke (IS) and peripheral arterial occlusive disease (PAOD); and venous thromboembolism (VTE). So far, the discussion on how much CVD and VTE share and differ in terms of pathological mechanisms has been based on morphological studies about the composition of venous and arterial thrombi, epidemiological studies about the association and common risk factors of CVD and VTE, and inferences upon the cellular and molecular mechanisms of each of these conditions. Objective: Here we introduce a new strategy to obtain insights on the association of CVD and VTE based on the comparison of transcriptomic signatures associated with these conditions. Methods: publicly available datasets (from Gene Expression Omnibus Database) of gene expression data from patients with AMI, IS, PAOD, cardioembolic stroke (CS), and VTE were identified and retrieved. Stringent selection criteria regarding patient selection, microarray methods and RNA sources were applied to limit heterogeneity as much as possible. A meta-analysis was performed using a robust statistical method, allowing the identification of genes that are commonly expressed in the same direction in all five conditions. We also identified a list of genes that were divergently expressed between VTE and CVD. Both lists were then used for functional and correlation analyses aimed to gain additional insights on the molecular pathogenesis of arterial and venous thrombosis. Results: Five datasets fulfilled the inclusion criteria and were included in our analyses: the dataset of VTE patients originally compared gene expression levels in patients with single or recurrent VTE with healthy controls (GSE19151); three datasets involving CVD compared gene expression levels of patients with PAOD (GSE 27034), AMI (GSE 48060) and IS (GSE 22255) with study-specific healthy controls. A dataset comparing patients with CS (GSE58294) and healthy controls was also included. In total, data from 163 adult patients and 145 healthy controls were analyzed. The meta-analysis generated a list of 473 genes whose expression was changed in the same direction in all five conditions (168 up-regulated and 305 down-regulated). The top 20 up- and down-regulated genes are shown in figure 1a. The functional analysis of the 168 up-regulated genes identified pathways associated with hemostasis, innate immunity and neutrophil activation and degranulation as overrepresented in patients compared to controls. When gene expression fold-change levels were analyzed across all five diseases, a lower correlation coefficient was observed between VTE and CVD, when compared to correlations observed within CVD such as AMI and PAOD (fig.1b). Moreover, an unsupervised cluster analysis showed that the expression pattern of these 473 genes in AMI, PAOD and IS are more closely related to each other than to VTE and CS (fig. 1a). When the 124 genes that were divergently expressed between VTE and CVD were functionally analyzed, genes that were upregulated only in CVD were associated with activation of innate immunity, whereas genes that were upregulated in VTE were associated with cell maintenance pathways. Discussion and conclusion: our comparative analyses provide new data on how venous and arterial thrombosis differ at a transcriptional level. Specifically, we identified a set of 473 genes whose expression levels were consistently changed in both CVD and VTE, and 124 genes with divergent expression levels between these conditions. The prominence of pathways associated with hemostasis, innate immunity and neutrophil function in both CVD and VTE are in line with the concept of immunothrombosis in the pathogenesis of thrombotic disorders. The clustering of MI, IS and PAOD compared to VTE and CS is coherent with the concept that CS is caused by thrombi formed in a different microenvironment than IS. Additional studies are warranted on the role of these genes and pathways in the pathogenesis of CVD and VTE, as well as on the biological relevance of these thrombosis-specific gene expression signatures in other thrombotic disorders. [Display omitted] DisclosuresDe Paula:Hematology and Transfusion Medicine Center, University of Campinas: Employment.