scholarly journals PRTN3/FCER1A Transcriptomic Ratio Predicts Hospitalization in Primary Care Attenders With Respiratory Infection

Author(s):  
Carmen Herrero-Rodríguez ◽  
Raquel Almansa ◽  
Amanda de la Fuente ◽  
Misericordia Martínez-Huélamo ◽  
Maria Pilar Vicente-Andres ◽  
...  

Abstract Early detection of patients with respiratory infection at risk of deteriorating could help to improve their outcome by facilitating immediate transfer to the hospital to receive the adequate level of care. In this regard, gene expression profiling is emerging as a promising tool to identify patients with infection at risk of suffering a complicated outcome. In a cohort of patients with respiratory infection attending to an Emergency Room at a community health centre, we quantified expression levels in blood of five genes involved in the granulocyte biology that have been previously described to be linked to infection severity: MMP8 (matrix metallopeptidase 8), LCN2 (lipocalin-2), LTF (lactotransferrin) and PRTN3 (proteinase 3) and FCER1A (receptor for Fc fragment of IgE, high affinity I). Expression levels of these genes were evaluated to predict hospitalization. Multivariate analysis adjusted by the National Early Warning Score (NEWS), neurovascular disease, hypertension and age revealed that all these genes independently predicted hospitalization. Nonetheless, the ratio between PRTN3/FCER1A outperformed individual genes to predict necessity of hospitalization (OR [CI95%], p: 8.36 [2.02-34.52],0.003). In conclusion, quantification of PRTN3/FCER1A gene expression ratio could represent a useful test to early identify those patients with respiratory infection at risk of deterioration in extra-hospital settings.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16583-e16583
Author(s):  
Richard C. Lauer ◽  
Marc Barry ◽  
Jin Wu ◽  
Ji-Hyun Lee ◽  
Dennis J. McCance ◽  
...  

e16583 Background: There is an urgent need to differentiate from truly localized prostate cancer and micrometastatic disease. PCA3 is an FDA-approved biomarker for prostate cancer; however, it is not a predictor of metastasis behavior. We have recently identified PRUNE2 as an unrecognized tumor suppressor gene. Here we examined if the ratio of PRUNE2 and its corresponding dominant-negative oncogene PCA3 might serve as a better predictor of the metastatic potential of prostate cancer, compared to PCA3alone. Methods: We studied 105 prostate cancer patients who underwent a radical prostatectomy at UNM Hospital from 2001 to 2009. At the time of prostatectomy, these patients had a Gleason score of 7 and organ-confined disease. They had at least 5-year follow-up for disease recurrence, and 19 patients developed recurrent disease. PCA3 and PRUNE2 gene expression was quantified by qRT-PCR and normalized to housekeeping control genes. Each experiment was carried out in triplicates. The Wilcoxon rank sum test was used to evaluate whether or not the difference in gene expression of PRUNE2 or PCA3 or the gene expression ratio ( PRUNE2/ PCA3), between patients with and without recurrence, was significant. The association between the time to recurrence and expression levels of each single gene or ratio were also analyzed by the Kaplan-Meier method along with log-rank test and the COX PH modeling. Results: There was no significant difference in expression levels of PRUNE2, PCA3, or the ratio PRUNE2/ PCA3, between patients who developed recurrent disease relative to those who did not. Conclusions: PRUNE2 and PCA3 expression levels, as well as PRUNE2/ PCA3 ratio, did not predict the metastatic potential of Gleason 7 prostate cancer in our retrospective patient cohort. We postulated that the deregulation of the molecular axis of PRUNE2 and PCA3 might occur early in the development of prostate cancer. We are currently examining this mechanistic hypothesis in other studies. [Table: see text]


2015 ◽  
Vol 145 (3-4) ◽  
pp. 253-264 ◽  
Author(s):  
Taejoon Kwon

Xenopus is an important model organism for the study of genome duplication in vertebrates. With the full genome sequence of diploid Xenopus tropicalis available, and that of allotetraploid X. laevis close to being finished, we will be able to expand our understanding of how duplicated genes have evolved. One of the key features in the study of the functional consequence of gene duplication is how their expression patterns vary across different conditions, and RNA-seq seems to have enough resolution to discriminate the expression of highly similar duplicated genes. However, most of the current RNA-seq analysis methods were not designed to study samples with duplicate genes such as in X. laevis. Here, various computational methods to quantify gene expression in RNA-seq data were evaluated, using 2 independent X. laevis egg RNA-seq datasets and 2 reference databases for duplicated genes. The fact that RNA-seq can measure expression levels of similar duplicated genes was confirmed, but long paired-end reads are more informative than short single-end reads to discriminate duplicated genes. Also, it was found that bowtie, one of the most popular mappers in RNA-seq analysis, reports significantly smaller numbers of unique hits according to a mapping quality score compared to other mappers tested (BWA, GSNAP, STAR). Calculated from unique hits based on a mapping quality score, both expression levels and the expression ratio of duplicated genes can be estimated consistently among biological replicates, demonstrating that this method can successfully discriminate the expression of each copy of a duplicated gene pair. This comprehensive evaluation will be a useful guideline for studying gene expression of organisms with genome duplication using RNA-seq in the future.


2016 ◽  
Vol 31 (3) ◽  
pp. 309-316
Author(s):  
Edyta Wieczorek ◽  
Michal Galicki ◽  
Bartlomiej Tomasik ◽  
Magdalena Krol ◽  
Ewa Jablonska ◽  
...  

Purpose An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast. Materials and methods Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA. Results In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013). Conclusions These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.


2014 ◽  
Vol 23 (03) ◽  
pp. 207-211
Author(s):  
C. Kasch ◽  
A. Osterberg ◽  
Thordis Granitzka ◽  
T. Lindner ◽  
M. Haenle ◽  
...  

SummaryThe RANK/RANKL/OPG system plays an important role in the regulation of bone metabolism and bony integration around implants. The aim of this study was to analyse gene expression of OPG, RANK, and RANKL in regenerating bone during implant integration. Additionally, the effect of intermittent para - thyroid hormone (PTH) treatment was analysed. A titanium chamber was implanted in the proximal tibiae of 48 female rats. The animals received either human PTH or saline solution (NaCl). After 21 and 42 days, RNA was isolated from tissue adjacent to the implant and expression of RANK, RANKL, and OPG was analysed. After 21 days, very low expression levels of all genes were shown. In contrast, increased gene expression after 42 days was determined. Expression of RANK and RANKL was lower than that for OPG. The lower expression levels after 21 days might be due to still ossifying, fibrotic tissue around the titanium chamber. An increased OPG synthesis rate associated with decreased RANKL expression after 42 days revealed bone-forming processes. Despite significant differences in gene expression between the time points, only slight differences were observed between application of intermittent PTH and NaCl after a period of 42 days.


2020 ◽  
Vol 27 (17) ◽  
pp. 2826-2839 ◽  
Author(s):  
Roberta Caputo ◽  
Daniela Cianniello ◽  
Antonio Giordano ◽  
Michela Piezzo ◽  
Maria Riemma ◽  
...  

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician’s decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).


2020 ◽  
Vol 20 (7) ◽  
pp. 518-523
Author(s):  
Rugül Köse Çinar

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.


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