Gene Expression Patterns Distinguish Mortality Risk in Patients with Postsurgical Shock

Nowadays, mortality rates in intensive care units are the highest of all hospital units. However, there is not a reliable prognostic system to predict the likelihood of death in patients with postsurgical shock. Thus, the aim of the present work is to obtain a gene expression signature to distinguish the low and high risk of death in postsurgical shock patients. In this sense, mRNA levels were evaluated by microarray on a discovery cohort to select the most differentially expressed genes between surviving and non-surviving groups 30 days after the operation. Selected genes were evaluated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort to validate the reliability of data. A receiver-operating characteristic analysis with the area under the curve was performed to quantify the sensitivity and specificity for gene expression levels, which were compared with predictions by established risk scales, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA). IL1R2, CD177, RETN, and OLFM4 genes were upregulated in the non-surviving group of the discovery cohort, and their predictive power was confirmed in the validation cohort. This work offers new biomarkers based on transcriptional patterns to classify the postsurgical shock patients according to low and high risk of death. The results present more accuracy than other mortality risk scores.

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Gene expression analysis of the pro-oestrous-stage rat uterus reveals neuroligin 2 as a novel steroid-regulated gene

Reproduction Fertility and Development ◽

10.1071/rd04040 ◽

2004 ◽

Vol 16 (8) ◽

pp. 763 ◽

Cited By ~ 8

Author(s):

Han-Seung Kang ◽

Chae-Kwan Lee ◽

Ju-Ran Kim ◽

Seong-Jin Yu ◽

Sung-Goo Kang ◽

...

Keyword(s):

Gene Expression ◽

Northern Blot ◽

Blot Analysis ◽

Northern Blot Analysis ◽

Expression Profiles ◽

Expression Patterns ◽

Oestrous Cycle ◽

Mrna Levels ◽

Rat Uterus ◽

Ovx Rats

In the present study, differential gene expression in the uteri of ovariectomised (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA expression array analysis. Differential uterine gene expression in OVX rats and progesterone (P4)-injected OVX rats (OVX v. OVX + P4 pair) was also examined. The uterine gene expression profiles of these two sets of animals were also compared for the effects of P4 treatment. RNA samples were extracted from uterine tissues and reverse transcribed in the presence of [α32P]-dATP. Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot analysis was used to validate the relative gene expression patterns obtained from the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two-fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes were upregulated during pro-oestrus compared with their expression in the OVX rat uterus. In the OVX v. OVX + P4 pair, 22 genes showed significant (>two-fold) changes in gene expression. Twenty of these genes were upregulated in the OVX + P4 animals. The genes for nuclear factor I–XI, afadin, neuroligin 2, semaphorin Z, calpain 4, cyclase-associated protein homologue, thymosin β-4X and p8 were significantly upregulated in the uteri of the pro-oestrus and OVX + P4 rats of both experimental pairs compared with the OVX rat uteri. These genes appear to be under the control of P4. One of the most interesting findings of the present study is the unexpected and marked expression of the neuroligin 2 gene in the rat uterus. This gene is expressed at high levels in the central nervous system and acts as a nerve cell adhesion factor. According to Northern blot analysis, neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus stages than during the oestrus and dioestrus stages of the oestrous cycle. In addition, neuroligin 2 mRNA levels were increased by both 17β-oestradiol (E2) and P4, although P4 administration upregulated gene expression to a greater extent than injection of E2. These results indicate that neuroligin 2 gene expression in the rat uterus is under the control of both E2 and P4, which are secreted periodically during the oestrous cycle.

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Establishment of a novel scoring model for mortality risk prediction in HIV-infected patients with cryptococcal meningitis

10.21203/rs.3.rs-366320/v1 ◽

2021 ◽

Author(s):

Ting Zhao ◽

Xiao-Lei Xu ◽

Jing-Min Nie ◽

Xiao-Hong Chen ◽

Zhong-Sheng Jiang ◽

...

Keyword(s):

High Risk ◽

Risk Prediction ◽

Mortality Risk ◽

Cryptococcal Meningitis ◽

Area Under Curve ◽

The Novel ◽

Multicenter Cohort Study ◽

Scoring Model ◽

Risk Of Death ◽

Prediction Probability

Abstract Purpose: Cryptococcal meningitis (CM) remains a leading cause of death in HIV-infected patients, despite advances in CM diagnostic and therapeutic strategies. This study was performed with the aim to develop and validate a novel scoring model to predict mortality risk in HIV-infected patients with CM (HIV/CM).Methods: Data on HIV/CM inpatients were obtained from a Multicenter Cohort study in China. Independent risk factors associated with mortality were identified based on data from 2013 to 2017, and a novel scoring model for mortality risk prediction was established. The prediction probability of the novel model was evaluated and verified using data from 2018 to 2020.Results: We found that six predictors, including age, stiff neck, impaired consciousness, intracranial pressure, CD4+ T-cell count, and urea levels, were associated with poor prognosis in HIV/CM patients. The novel scoring model could effectively identify HIV/CM patients at high risk of death on admission (area under curve 0.876; p＜0.001). When the cut-off value of 5.5 points or more was applied, the sensitivity and specificity was 74.1% and 83.8%, respectively. Additionally, our scoring model showed a good discriminatory ability in the validation cohort (area under curve 0·886; p＜0.001).Conclusions: Our developed scoring model of six variables is simple, convenient, and accurate for screening high-risk patients with HIV/CM, which may be a useful tool for physicians to assess prognosis in HIV/CM inpatients.

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GDF-9 and BMP-15 mRNA Levels in Canine Cumulus Cells Related to Cumulus Expansion and the Maturation Process

Animals ◽

10.3390/ani10030462 ◽

2020 ◽

Vol 10 (3) ◽

pp. 462 ◽

Cited By ~ 3

Author(s):

George Ramirez ◽

Jaime Palomino ◽

Karla Aspee ◽

Monica De los Reyes

Keyword(s):

Gene Expression ◽

Estrous Cycle ◽

Expression Patterns ◽

Cumulus Cells ◽

Mrna Levels ◽

Cumulus Expansion ◽

Polymerase Chain ◽

Specific Regulation ◽

Reproductive Phases

The competence to undergo expansion is a characteristic of cumulus cells (CCs). The aim was to investigate the expression of GDF-9 and BMP-15 mRNA in canine cumulus cells in relation to cumulus expansion and meiotic development over the estrous cycle. CCs were recovered from nonmatured and in vitro-matured (IVM) dog cumulus oocyte complexes (COCs), which were obtained from antral follicles at different phases of the estrous cycle. Quantitative real-time polymerase chain reaction (q-PCR) was used to evaluate the relative abundance of GDF-9 and BMP-15 transcripts from the CCs with or without signs of expansion. The results were evaluated by ANOVA and logistic regression. The maturity of the oocyte and the expansion process affected the mRNA levels in CCs. There were differences (p < 0.05) in GDF-9 and BMP-15 gene expression in CCs isolated from nonmatured COCs when comparing the reproductive phases. Lower mRNA levels (p < 0.05) were observed in anestrus and proestrus in comparison to those in estrus and diestrus. In contrast, when comparing GDF-9 mRNA levels in IVM COCs, no differences were found among the phases of the estrous cycle in expanded and nonexpanded CCs (p < 0.05). However, the highest (p < 0.05) BMP-15 gene expression in CCs that did not undergo expansion was exhibited in anestrus and the lowest (p < 0.05) expression was observed in estrus in expanded CCs. Although the stage of the estrous cycle did not affect the second metaphase (MII )rates, the expanded CCs obtained at estrus coexisted with higher percentages of MII (p < 0.05). In conclusion, the differential expression patterns of GDF-9 and BMP-15 mRNA transcripts might be related to cumulus expansion and maturation processes, suggesting specific regulation and temporal changes in their expression.

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Identification and validation of a potent multi-mRNA signature for the prediction of early relapse in hepatocellular carcinoma

Carcinogenesis ◽

10.1093/carcin/bgz018 ◽

2019 ◽

Vol 40 (7) ◽

pp. 840-852 ◽

Cited By ~ 3

Author(s):

Jie Cai ◽

Ying Tong ◽

Lifeng Huang ◽

Lei Xia ◽

Han Guo ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Messenger Rna ◽

Validation Cohort ◽

Expression Profiles ◽

External Validation ◽

Early Recurrence ◽

Discovery Cohort ◽

Early Relapse ◽

Staging Systems

Abstract Early recurrence of hepatocellular carcinoma (HCC) is implicated in poor patient survival and is the major obstacle to improving prognosis. The current staging systems are insufficient for accurate prediction of early recurrence, suggesting that additional indicators for early recurrence are needed. Here, by analyzing the gene expression profiles of 12 Gene Expression Omnibus data sets (n = 1533), we identified 257 differentially expressed genes between HCC and non-tumor tissues. Least absolute shrinkage and selection operator regression model was used to identify a 24-messenger RNA (mRNA)-based signature in discovery cohort GSE14520. With specific risk score formula, patients were divided into high- and low-risk groups. Recurrence-free survival within 2 years (early-RFS) was significantly different between these two groups in discovery cohort [hazard ratio (HR): 7.954, 95% confidence interval (CI): 4.596–13.767, P < 0.001], internal validation cohort (HR: 8.693, 95% CI: 4.029–18.754, P < 0.001) and external validation cohort (HR: 5.982, 95% CI: 3.414–10.480, P < 0.001). Multivariable and subgroup analyses revealed that the 24-mRNA-based classifier was an independent prognostic factor for predicting early relapse of patients with HCC. We further developed a nomogram integrating the 24-mRNA-based signature and clinicopathological risk factors to predict the early-RFS. The 24-mRNA-signature-integrated nomogram showed good discrimination (concordance index: 0.883, 95% CI: 0.836–0.929) and calibration. Decision curve analysis demonstrated that the 24-mRNA-signature-integrated nomogram was clinically useful. In conclusion, our 24-mRNA signature is a powerful tool for early-relapse prediction and will facilitate individual management of HCC patients.

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1077 – A Novel Gene Expression Signature for the Diagnosis of High-Risk, Hepatocellular Carcinoma Patients with Rapidly Growing Tumors

Gastroenterology ◽

10.1016/s0016-5085(19)37362-7 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-227

Author(s):

Takeo Toshima ◽

Jasjit K. Banwait ◽

Hideo Baba ◽

Tomoharu Yoshizumi ◽

Masaki Mori ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

High Risk ◽

Gene Expression Signature ◽

Expression Signature ◽

Novel Gene

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FOXA1 in breast cancer

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399409001008 ◽

2009 ◽

Vol 11 ◽

Cited By ~ 39

Author(s):

Harikrishna Nakshatri ◽

Sunil Badve

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Transcription Factor ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Gene Expression Signature ◽

Specific Gene ◽

Breast Cancers ◽

Transcription Factor Network ◽

Histopathological Classification

Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.

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An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML

Blood ◽

10.1182/blood-2007-09-115055 ◽

2008 ◽

Vol 111 (9) ◽

pp. 4490-4495 ◽

Cited By ~ 63

Author(s):

Lars Bullinger ◽

Konstanze Döhner ◽

Raphael Kranz ◽

Christoph Stirner ◽

Stefan Fröhling ◽

...

Keyword(s):

Gene Expression ◽

Clinical Outcome ◽

Dna Microarrays ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Signature ◽

Normal Karyotype ◽

Mutation Status ◽

Signature Genes ◽

Starting Point

Abstract Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3-ITD mutation and to evaluate the utility of a FLT3 signature for prognostication. DNA microarrays were used to profile gene expression in a training set of 65 NK-AML cases, and supervised analysis, using the Prediction Analysis of Microarrays method, was applied to build a gene expression–based predictor of FLT3-ITD mutation status. The optimal predictor, composed of 20 genes, was then evaluated by classifying expression profiles from an independent test set of 72 NK-AML cases. The predictor exhibited modest performance (73% sensitivity; 85% specificity) in classifying FLT3-ITD status. Remarkably, however, the signature outperformed FLT3-ITD mutation status in predicting clinical outcome. The signature may better define clinically relevant FLT3 signaling and/or alternative changes that phenocopy FLT3-ITD, whereas the signature genes provide a starting point to dissect these pathways. Our findings support the potential clinical utility of a gene expression–based measure of FLT3 pathway activation in AML.

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PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1819534116 ◽

2019 ◽

Vol 116 (14) ◽

pp. 7033-7042 ◽

Cited By ~ 20

Author(s):

Joshua Hatterschide ◽

Amelia E. Bohidar ◽

Miranda Grace ◽

Tara J. Nulton ◽

Hee Won Kim ◽

...

Keyword(s):

Gene Expression ◽

Human Papillomavirus ◽

High Risk ◽

Gene Expression Signature ◽

Human Keratinocytes ◽

Keratinocyte Differentiation ◽

Oncogenic Transformation ◽

Hpv E7 ◽

Oncogenic Activity ◽

High Risk Hpv

High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion ofPTPN14from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation andPTPN14deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV+but not HPV−cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.

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A Prognostic Gene-Expression Signature and Risk Score for Meningioma Recurrence After Resection

Neurosurgery ◽

10.1093/neuros/nyaa355 ◽

2020 ◽

Vol 88 (1) ◽

pp. 202-210 ◽

Cited By ~ 1

Author(s):

William C Chen ◽

Harish N Vasudevan ◽

Abrar Choudhury ◽

Melike Pekmezci ◽

Calixto-Hope G Lucas ◽

...

Keyword(s):

Gene Expression ◽

Risk Score ◽

Gene Expression Analysis ◽

Validation Cohort ◽

Gene Expression Signature ◽

Gene Signature ◽

Who Grade ◽

Independent Validation ◽

Meningioma Recurrence ◽

Targeted Gene Expression

Abstract BACKGROUND Prognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy. OBJECTIVE To identify a prognostic gene signature for meningioma recurrence and mortality after resection using targeted gene-expression analysis. METHODS Targeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence. RESULTS We identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P < .001 vs .09, log-rank test), shorter time to failure (TTF, F-test, P < .0001), and overall survival (OS, P < .0001 vs .07) and was independently associated with worse LFFR (relative risk [RR] 1.56, 95% CI 1.30-1.90) and OS (RR 1.32, 95% CI 1.07-1.64), after adjusting for clinical covariates. When tested on an independent validation cohort, the gene-signature risk score remained associated with shorter TTF (F-test, P = .002), compared favorably to WHO grade in stratifying cases by OS (P = .003 vs P = .10), and was significantly associated with worse OS (RR 1.86, 95% CI 1.19-2.88) on multivariate analysis. CONCLUSION The prognostic meningioma gene-expression signature and risk score presented may be useful for identifying patients at risk for recurrence.

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Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

Mediators of Inflammation ◽

10.1155/2013/684237 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Rohini Mehta ◽

Aybike Birerdinc ◽

Arpan Neupane ◽

Amirhossein Shamsaddini ◽

Arian Afendy ◽

...

Keyword(s):

Gene Expression ◽

Hepatic Fibrosis ◽

Interleukin 1 ◽

Expression Patterns ◽

Interleukin 8 ◽

Morbidly Obese ◽

Low Grade ◽

Mrna Levels ◽

Gastric Tissue ◽

Hepatic Inflammation

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

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