Molecular predictors of response to selinexor in advanced unresectable de-differentiated liposarcoma (DDLS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11509-11509
Author(s):  
Christopher James Walker ◽  
Hua Chang ◽  
Jianjun Liu ◽  
Bruno Vincenzi ◽  
Andrea Napolitano ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
B Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Tumor Control ◽  
Double Blind Study ◽  
Sequencing Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Validation Set

11509 Background: Patients (pts) with recurrent inoperative DDLS have a poor prognosis and limited treatment options. Selinexor is an oral, selective inhibitor of nuclear export (SINE) compound approved for previously treated pts with myeloma and diffuse large B-cell lymphoma. SEAL was a Phase 2-3 randomized, double-blind, study of selinexor versus placebo in pts with progressive DDLS and 2-5 prior systemic therapies. SEAL showed significantly prolonged progression-free survival (PFS, HR = 0.70, p = 0.0228) with well managed toxicity. A biomarker predictive of clinical activity could be used to optimize selection of pts with DDLS for selinexor. Methods: Pts were randomized 2:1 for Phase 3: 188 received twice weekly selinexor (60mg) and 97 received placebo. Three exploratory biomarker analyses (RNA sequencing of biopsies) from selinexor-treated pts were performed: discovery set of sensitive (n = 8) or resistant (n = 9) tumors; a validation set of pts with favorable (n = 19) or poor (n = 14) tumor control based on PFS, and paired lesions from a pt who harbored both a responsive and resistant lesion. Tumor biopsies from 24 pts on placebo with short ( < 5 months, n = 18) and long ( > 6 months, n = 6) PFS were RNA sequenced. Gene expressions were compared using a negative binomial distribution with DeSeq2. Pathway analyses were performed using Gene Set Enrichment Analysis (GSEA) with MSigDB Cancer Gene Neighborhoods. Results: RNA sequencing analysis comparing 17 sensitive and resistant tumors identified 114 differentially expressed genes (adjusted p-values < 0.05). Expression of CALB1, which encodes the calcium-binding protein calbindin, was significantly lower in sensitive tumors (adjusted P [Padj] = 7.5x10-20), and expression of GRM1, which encodes a metabotropic glutamate receptor that activates phospholipase C, was higher in selinexor sensitive tumors (Padj= 0.003). These findings were confirmed in an independent validation set (Padj = 0.01 – 0.02). In the pt with paired sensitive and resistant lesions, CALB1 expression was 52-fold lower in the sensitive tumor. In a comparison of placebo-treated pts, neither CALB1 or GRM1 was differentially expressed between pts with short or long PFS, indicating they are markers of response to selinexor treatment, rather than general markers of disease aggressiveness. Gene set enrichment analyses revealed that selinexor sensitive tumors in the discovery and validation sets showed upregulation of cancer genes related to SNRK and the netrin 1 receptor tumor suppressor DCC. The resistant tumors showed upregulated EIF3S2 translation initiator-related genes. Conclusions: Selinexor sensitive DDLS tumors showed low expression of CALB1 and high GRM1. If validated, pts with DDLS whose tumors match this expression profile are especially likely to benefit from selinexor. Clinical trial information: NCT02606461.

scholarly journals Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

2018 ◽  
Vol 314 (4) ◽  
pp. L617-L625 ◽  
Author(s):  
Arjun Mohan ◽  
Anagha Malur ◽  
Matthew McPeek ◽  
Barbara P. Barna ◽  
Lynn M. Schnapp ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Murine Model ◽  
Alveolar Macrophages ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Multiwall Carbon Nanotube ◽  
Gene Set Enrichment ◽  
Integrated Network ◽  
Gene Set ◽  
Gene Sets

To advance our understanding of the pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)-based murine model that shows marked histological and inflammatory signal similarities to this disease. In this study, we compared the alveolar macrophage transcriptional signatures of our animal model with human sarcoidosis to identify overlapping molecular programs. Whole genome microarrays were used to assess gene expression of alveolar macrophages in six MWCNT-exposed and six control animals. The results were compared with the transcriptional profiles of alveolar immune cells in 15 sarcoidosis patients and 12 healthy humans. Rigorous statistical methods were used to identify differentially expressed genes. To better elucidate activated pathways, integrated network and gene set enrichment analysis (GSEA) was performed. We identified over 1,000 differentially expressed between control and MWCNT mice. Gene ontology functional analysis showed overrepresentation of processes primarily involved in immunity and inflammation in MCWNT mice. Applying GSEA to both mouse and human samples revealed upregulation of 92 gene sets in MWCNT mice and 142 gene sets in sarcoidosis patients. Commonly activated pathways in both MWCNT mice and sarcoidosis included adaptive immunity, T-cell signaling, IL-12/IL-17 signaling, and oxidative phosphorylation. Differences in gene set enrichment between MWCNT mice and sarcoidosis patients were also observed. We applied network analysis to differentially expressed genes common between the MWCNT model and sarcoidosis to identify key drivers of disease. In conclusion, an integrated network and transcriptomics approach revealed substantial functional similarities between a murine model and human sarcoidosis particularly with respect to activation of immune-specific pathways.

scholarly journals Blood and Brain Transcriptome Analysis Reveals APOE Genotype-mediated and Immune-related Pathways Involved in Alzheimer Disease

2021 ◽  
Author(s):  
Rebecca Panitch ◽  
Junming Hu ◽  
Weiming Xia ◽  
David A Bennett ◽  
Thor D Stein ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Blood Brain Barrier ◽  
Vascular Injury ◽  
Apoe Genotype ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Brain Barrier ◽  
Gene Set Enrichment ◽  
Gene Set

Abstract Background: While Alzheimer disease (AD) is generally considered as a brain disorder, blood biomarkers may be useful for diagnosis and prediction of AD brain pathology. The APOE ε4 allele has shown cerebrovascular effects including acceleration of blood brain barrier breakdown. Methods: We evaluated differential expression of previously established AD genes in brains from 344 pathologically confirmed AD cases and 232 controls and in blood from 112 pathologically confirmed AD cases and 67 controls from the Religious Orders Study and Memory and Aging Project. Differential gene expression between AD cases and controls was analyzed in the blood and brain jointly using a multivariate approach in the total sample and within APOE genotype groups. Gene set enrichment analysis was performed within APOE genotype groups using the results from the combined blood and brain analyses to identify biologically important pathways. Gene co-expression networks in brain and blood samples were investigated using weighted correlation network analysis. Top ranked genes from networks and pathways were further evaluated with vascular injury traits. Results: We observed differentially expressed genes with P<0.05 in both brain and blood for established AD genes INPP5D (upregulated) and HLA-DQA1 (downregulated). PIGHP1 and FRAS1 were differentially expressed at the transcriptome-wide level (P<3.3x10 -6 ) within ε2/ε3 and ε3/ε4 groups, respectively. Gene-set enrichment analysis revealed 21 significant pathways (false discovery rate P<0.05) in at least one APOE genotype group. Ten pathways were significantly enriched in the ε3/ε4 group, and six of these were unique to these subjects. Four pathways were enriched for AD upregulated genes in the ε3/ε4 group and AD downregulated genes in ε4 lacking subjects. We identified a co-expressed gene network in brain that reproduced in blood and showed higher average expression in ε4 carriers. Twenty-three genes from pathway and network analyses were significantly associated at P<0.05 with at least one vascular injury trait. Conclusion: These results suggest that APOE genotype contributes to unique expression network profiles in both blood and brain. Several genes in these networks are associated with measures of vascular injury and potentially contribute to ε4’s effect on the blood brain barrier.

scholarly journals Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive treatment

2020 ◽  
Vol 35 (8) ◽  
pp. 1875-1888
Author(s):  
D A Crosby ◽  
L E Glover ◽  
E P Brennan ◽  
P Kelly ◽  
P Cormican ◽  
...  
Keyword(s):  
Study Design ◽  
Enrichment Analysis ◽  
Unexplained Infertility ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Discovery Cohort ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Assisted Reproductive Treatment ◽  
Support Fund

Abstract STUDY QUESTION Which transcriptomic alterations in mid-luteal endometrial scratch biopsies, taken prior to the assisted reproductive treatment (ART) treatment cycle are associated with unsuccessful pregnancy? SUMMARY ANSWER Dysregulated interleukin-17 (IL-17) pathway components are demonstrated in women who fail to become pregnant after ART. WHAT IS KNOWN ALREADY Implantation failure is now recognised as a critical factor in unexplained infertility and may be an important component of failed ART. STUDY DESIGN, SIZE, DURATION Using a prospective longitudinal study design, 29 nulliparous women with unexplained infertility undergoing ART were recruited between October 2016 and February 2018. Mid-luteal stage endometrium and matched serum samples were collected, and patients underwent a single embryo transfer in the subsequent cycle. RNA-seq analysis of endometrial biopsies was performed on the discovery cohort (n = 20). PARTICIPANTS/MATERIALS, SETTING, METHODS Gene set enrichment analysis of the differentially expressed genes (DEGs) was performed. Endometrium and serum were then prepared for IL-17A analysis by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE There were 204 differentially expressed protein-coding genes identified in tissue from women who became pregnant (n = 9) compared with tissue from women who failed to become pregnant (n = 11) (false discovery rate; P &lt; 0.05). Of the 204 DEGs, 166 were decreased while 38 were increased in the pregnant compared to the non-pregnant groups. Gene set enrichment analysis of the DEGs identified an over-representation of IL-17 and Pl3K-Akt signalling pathways. All the DEGs within the IL-17 signalling pathway (MMP3, MMP1, IL1β, LCN2, S100A9 and FOSL1) demonstrated decreased expression in the pregnant group. Serum IL-17 protein levels were increased in the non-pregnant discovery cohort (n = 11) and these findings were confirmed a validation cohort (n = 9). LIMITATIONS, REASONS FOR CAUTION Limitations of our study include the cohort size and the lack of aneuploidy data for the embryos; however, all embryos transferred were single good or top-quality blastocysts. WIDER IMPLICATIONS OF THE FINDINGS These findings demonstrate dysregulated IL-17 pathway components in women who fail to become pregnant after ART. Elevated serum levels of the pro-inflammatory cytokine IL-17 may predict failure of ART in women with unexplained infertility. Future trials of anti-IL-17 therapies in this cohort warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S) Funding from the UCD Wellcome Institutional Strategic Support Fund, which was financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership (ref 204844/Z/16/Z), is acknowledged. The authors have no competing interests. TRIAL REGISTRATION NUMBER NA.

Gene expression in prostate tissue according to frequency of ejaculation.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 25-25
Author(s):  
Jennifer R. Rider ◽  
Jennifer A Sinnott ◽  
Lorelei A. Mucci
Keyword(s):  
Gene Expression ◽  
Normal Tissue ◽  
Tumor Tissue ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Adjacent Normal Tissue ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Ejaculation Frequency

25 Background: Long-term prospective data from within the Health Professionals Follow-up Study (HPFS) suggest more frequent ejaculation throughout adult life may be protective against future development of prostate cancer (PCa). Compared to men with an average monthly ejaculation frequency (EF) of 4-7 times/month during adulthood, men who ejaculated at least 21 times per month were 30% less likely to be diagnosed with PCa after adjustment for a number of potential confounders and PCa screening. We sought to explore mechanisms through which EF may influence PCa development utilizing gene expression data assessed on tumor and adjacent normal tissue. Methods: In 1992, 31,925 HPFS participants were questioned on their average monthly EF at ages 20-29, 40-49, and in the previous year; 3,839 of these men were later diagnosed with PCa. Expression of 20,254 genes was available from archival tumor tissue from 156 cases; 84 of these cases also had data from adjacent normal tissue. We regressed each gene expression value as a continuous outcome on EF, age at diagnosis, and year at diagnosis. We calculated the p value associated with the coefficient for the EF variable as a measure of the strength of the trend test. We then used t values for the coefficients to rank the genes, and ran a gene set enrichment analysis to identify pathways with genes associated with EF. Results: We observed that while there was not much signal in the tumor tissue, there was enrichment of smaller p values in the adjacent normal tissue. EF in the time period most proximal to diagnosis is most strongly associated with gene expression in normal tissue. Focusing on the association between gene expression in normal tissue and EF in the year prior to the questionnaire (1991), the top six differentially expressed genes were OR4K1, CCDC138, SERPINA9, TRMT61B, ZNF302, and ASB4. Gene set enrichment analysis revealed a substantial number of pathways differentially expressed at the FDR <0.05 threshold. Conclusions: Identifying changes in gene expression associated with EF in normal prostate tissue provides further support for a biological role of ejaculation frequency in the etiology of PCa. Notably, pathways downregulated with increasing ejaculation frequency were primarily immune related.

scholarly journals Prognostic Relevance of BRCA1 Expression in Survival of Patients With Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
E Sun Paik ◽  
Chi-Son Chang ◽  
Ye Lin Chae ◽  
So Young Oh ◽  
Sun-Ju Byeon ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Brca1 Expression ◽  
Gene Set Enrichment ◽  
Cox Regression Analysis ◽  
Gene Set ◽  
Prognostic Relevance

ObjectiveBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several cancers, the objective of this study was to investigate BRCA1 expression using immunohistochemistry (IHC) in cervical cancer and its possible prognostic relevance.MethodsSeventy patients with cervical cancer were enrolled in this study. Samples from each tumor were stained for BRCA1 and reviewed independently by gynecologic pathologists blinded to the BRCA status. Kaplan–Meier methods were used to estimate overall survival according to BRCA1 expression. Differentially expressed genes (DEGs) by BRCA1 expression were selected using GSE44001 dataset, which included 300 samples treated with radical hysterectomy. In addition, cox regression analysis with backward elimination was performed to select independent prognostic markers. Gene set enrichment analysis (GSEA) was done using these DEGs.ResultsBRCA1 IHC was positive in 62.9% (44/70) of cases. Patients with BRCA1 expression showed better overall survival (100% vs. 76.2%, HR 0.20, 95% CI 0.04 – 0.99, p = 0.028) than those without BRCA1 expression. Analysis of gene expression profiles according to BRCA1 expression identified 321 differentially expressed mRNAs. Gene set enrichment analysis results showed two dysregulated pathways (VEGF_A_UP.V1_DN and E2F1_UP.V1_UP). Of these DEGs, alterations of 20 gene signatures were found to be independently associated with survival outcomes of patients.ConclusionsBRCA1 expression in cervical cancer tissue is associated with survival. In addition, the identification of specific gene alterations associated with BRCA1 expression could help to provide individualized prediction in these patients.

scholarly journals HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 120
Author(s):  
Yiyun Sun ◽  
Dandan Xu ◽  
Chundong Zhang ◽  
Yitao Wang ◽  
Lian Zhang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Squamous Cell ◽  
Gene Pair ◽  
Gene List ◽  
Ectopic Expression ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Gene Set

We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remains obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from The Cancer Genome Atlas (TCGA) database using the correlation analysis of gene expression and gene set enrichment analysis (GSEA), which revealed that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited the Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected using RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2, and BUB1, was involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with the shorter overall survival of LSCC patients. Taken together, our results indicate that GLI1/2 mediates the expression of the PRR11-SKA2-centric gene set that serves as an unfavorable prognostic indicator for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC.

611 RNA-sequencing reveals a unique immune transcriptional landscape in the vaccine sites of patients with circulating T-cell responses to cancer immunization

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A646-A647
Author(s):  
Max Meneveau ◽  
Pankaj Kumar ◽  
Kevin Lynch ◽  
Karlyn Pollack ◽  
Craig Slingluff
Keyword(s):  
T Cell ◽  
Differentially Expressed Genes ◽  
T Cell Responses ◽  
Differentially Expressed ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Cell Responses ◽  
Vaccine Site ◽  
And Control ◽  
Transcriptional Landscape

BackgroundVaccines are a promising therapeutic for patients with advanced cancer, but achieving robust T-cell responses remains a challenge. Melanoma-associated antigen-A3 (MAGE-A3) in combination with adjuvant AS15 (a formulation of Toll-Like-Receptor (TLR)-4 and 9 agonists and a saponin), induced systemic CD4+ T-cell responses in 50% of patients when given subcutaneously/intradermally. Little is known about the transcriptional landscape of the vaccine-site microenvironment (VSME) of patients with systemic T-cell responses versus those without. We hypothesized that patients with systemic T-cell responses to vaccination would exhibit increased immune activation in the VSME, higher dendritic cell (DC) activation/maturation, TLR-pathway activation, and enhanced Th1 signatures.MethodsBiopsies of the VSME were obtained from participants on the Mel55 clinical trial (NCT01425749) who were immunized with MAGE-A3/AS15. Biopsies were taken 8 days after immunization. T-cell response to MAGE-A3 was assessed in PBMC after in-vitro stimulation with recMAGE-A3, by IFNγ ELISPOT assay. Gene expression was assessed by RNAseq using DESeq2. Comparisons were made between immune-responders (IR), non-responders (NR), and normal skin controls. FDR p<0.01 was considered significant.ResultsFour IR, four NR, and three controls were evaluated. The 500 most variable genes were used for principal component analysis (PCA). Two IR samples were identified as outliers on PCA and excluded from further analysis. There were 882 differentially expressed genes (DEGs) in the IR group vs the NR group (figure 1A). Unsupervised clustering of the top 500 DEGs revealed clustering according to the experimental groups (figure 1B). Of the 10 most highly upregulated DEGs, 9 were immune-related (figure 1C). Gene-set enrichment analysis revealed that immune-related pathways were highly enriched in IRs vs NRs (figure 1D). CD4 and CD8 expression did not differ between IR and NR (figure 2A), though both were higher in IR compared to control. Markers of DC activation/maturation were higher in IR vs NR (figure 2B), as were several Th1 associated genes (figure 2C). Interestingly, markers of exhaustion were higher in IR v NR (figure 2D). Expression of numerous TLR-pathway genes was higher in IR vs NR, including MYD88, but not TICAM1 (figure 2E).Abstract 611 Figure 1Gene expression profiling of vaccine site samples from patients immunized with MAGE-A3/AS15. (A) Volcano plots showing the distribution of differentially expressed genes (DEGs) between immune responders (IR) and non-responders (NR), IR and control, and NR and control. (B) Heatmap of the top 500 most differentially expressed genes demonstrating hierarchical clustering of sequenced samples according to IR, NR, and control. (C) Table showing the 10 most highly up and down-regulated genes in IR compared to NR. 9 of the top 10 most highly up-regulated genes are related to the immune response. (D) Enrichment plots from a gene set enrichment analysis highlighting the upregulation of immune related pathways in IR compared to NR. Gene set enrichment data was generated from the Reactome gene set database and included all expressed genes. Significance was set at FDR p <0.01Abstract 611 Figure 2Expression of T-cell markers in IR vs NR vs Control samples in the vaccine site microenvironment (VSME). (A) T-cell markers showing similar expression in IR vs NR but higher expression in IR vs control. (B) Markers of dendritic cell activation and maturation in the VSME which are higher in IR vs control but not IR vs NR. (B) Transcription factors and genes associated with Th1/Th2 responses within the VSME. (D) Genes associated with T-cell exhaustion at the VSME. (E) Expression of TLR pathway genes in the VSME. Expression data is provided in terms of normalized counts. Bars demonstrate median and interquartile range. N=9. IR = immune responder, NR = non-responder, TLR = Toll-like Receptor. * = <0.01, ** < 0.001, *** <0.0001, **** < 0.00001ConclusionsThese findings suggest a unique immune-transcriptional landscape in the VSME is associated with circulating T-cell responses to immunization, with differences in DC activation/maturation, Th1 response, and TLR signaling. Thus, immunologic changes in the VSME are useful predictors of systemic immune response, and host factors that modulate immune-related signaling at the vaccine site may have concordant systemic effects on promoting or limiting immune responses to vaccines.Trial RegistrationSamples for this work were collected from patients enrolled on the Mel55 clinical trial NCT01425749.Ethics ApprovalThis work was completed after approval from the UVA institutional review board IRB-HSR# 15398.

scholarly journals Higher Acid-Base Imbalance Associated with Respiratory Failure Could Decrease the Survival of Patients with Scrub Typhus during Intensive Care Unit Stay: A Gene Set Enrichment Analysis

2019 ◽  
Vol 8 (10) ◽  
pp. 1580 ◽  
Author(s):  
Kyoung Min Moon ◽  
Kyueng-Whan Min ◽  
Mi-Hye Kim ◽  
Dong-Hoon Kim ◽  
Byoung Kwan Son ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Failure ◽  
Scrub Typhus ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Acid Base ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Gene Sets

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.

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