scholarly journals Integrated Analysis of lncRNA-associated ceRNA Network Identifies Prognostic lncRNAs in Bladder Cancer Based on Whole Transcriptome Sequencing and TCGA Database

2021 ◽  
Author(s):  
Shiwei Xiao ◽  
Yigang Zuo ◽  
Yinglong Huang ◽  
Yanan Li ◽  
Dongbo Yuan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Transcriptome Sequencing ◽  
Risk Groups ◽  
Gene Signature ◽  
Stepwise Multiple Regression ◽  
Sequencing Data ◽  
Predicting Model ◽  
Whole Transcriptome Sequencing ◽  
Independent Risk Factors ◽  
Whole Transcriptome

Abstract BackgroundBladder cancer (BC) is a serious urinary tract malignancy with high incidences and deaths. Here, we aim to explore the OS-related lncRNAs and mRNAs, and constructed a reliable predicting model for accurately predict BC prognosis. Methods3 matched BC tumor samples and adjacent normal samples were processed by whole transcriptome sequencing. Differentially expressed lncRNAs and mRNAs (DE-lncRNAs and DE-mRNAs) were identified with the thresholds |log2 (FC) |>2 and p value <0.05 using DEGseq2 R package. Meantime, 408 BC samples and 19 normal samples were downloaded from TCGA database. And DE-lncRNAs and DE-mRNAs were screened with thresholds |log2(FC) |>0.5 and p value<0.05. The DE-lncRNAs and DE-mRNAs were overlapped between RNA-sequencing data and TCGA data. Then, overall survival (OS)-related DE-lncRNAs and DE-mRNAs were screened and a prognostic gene signature and risk model were constructed using Univariate Cox and stepwise multiple regression analysis. Risk score was calculated based on prognostic gene signature. The independent risk factors were identified with incorporation into clinical risk factors using Univariate Cox and stepwise multiple regression analysis. A predicting model was constructed based on independent factors, and calibrated using Time-dependent ROC curves. Finally, the differentially expressed genes (DEGs) between high-risk and low-risk groups were identified with thresholds |log2(FC) |>0.5 and p value<0.05. And the biofunction was determined by Gene Set Enrichment Analysis (GSEA). ResultsA total 2210 DE-lncTNAs and 2334 DE-mRNAs were identified based on whole transcriptome sequencing. And a total 3724 DE-lncRNAs and 2689 DE-mRNAs were identified based on TCGA database. Then, 137 DE-lncRNAs and 278 DE-mRNAs were screened by overlapping RNA sequencing data and TCGA data. A total 13 gene signature were identified to be closely related with OS in BC. Moreover, these 13-OS-related gene signature were identified as independent risk factors with clinical risk factors. Then, a nomogram was constructed and confirmed as the calibration and accuracy predicating model for OS in BC. Finally, a total 739 DEGs were identified between high-risk and low-risk groups, most of DEGs enriched in immune-related pathways. And an OS-related ceRNA network was selected based on 13-OS-related signature. ConclusionOur finding provided novel OS-related prognostic signature and reliable predicting model for BC patients, which might facilitate individualized treatment and prognostic evaluation.

scholarly journals Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS

2020 ◽  
Vol 4 (21) ◽  
pp. 5393-5401
Author(s):  
Anna Stengel ◽  
Rabia Shahswar ◽  
Torsten Haferlach ◽  
Wencke Walter ◽  
Stephan Hutter ◽  
...  
Keyword(s):  
Transcriptome Sequencing ◽  
Residual Disease ◽  
Fusion Transcript ◽  
Whole Genome Sequencing Data ◽  
Control Group ◽  
Complex Karyotype ◽  
Sequencing Data ◽  
Fusion Transcripts ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Abstract Fusion transcripts are frequent genetic abnormalities in myeloid malignancies and are often the basis for risk stratification, minimal residual disease (MRD) monitoring, and targeted therapy. We comprehensively analyzed the fusion transcript landscape in 572 acute myeloid leukemia (AML) and 630 myelodysplastic syndrome (MDS) patients by whole transcriptome sequencing (WTS). Totally, 274 fusion events (131 unique fusions) were identified in 210/572 AML patients (37%). In 16/630 MDS patients, 16 fusion events (15 unique fusions) were detected (3%). In AML, 141 cases comprised entity-defining rearrangements (51% of all detected fusions) and 21 (8%) additional well-known fusions, all detected by WTS (control group). In MDS, only 1 fusion was described previously (NRIP1-MECOM, n = 2). Interestingly, a high number of so-far unreported fusions were found (41% [112/274] in AML, 88% [14/16] in MDS), all validated by cytogenetic and/or whole genome sequencing data. With 1 exception (CTDSP1-CFLAR, n = 2), all novel fusions were observed in 1 patient each. In AML, cases with novel fusions showed concomitantly a high frequency of TP53 mutations (67%) and of a complex karyotype (71%), which was also observed in MDS, but less pronounced (TP53, 26%; complex karyotype, 21%). A functional annotation of genes involved in novel fusions revealed many functional relevant genes (eg, transcription factors; n = 28 in AML, n = 2 in MDS) or enzymes (n = 42 in AML, n = 9 in MDS). Taken together, new genomic alterations leading to fusion transcripts were much more common in AML than in MDS. Any novel fusions might be of use for developing markers (eg, for MRD monitoring), particularly in cases without an entity-defining abnormality.

scholarly journals O6: EARLY ANASTOMOTIC BILIARY COMPLICATIONS AFTER LIVER TRANSPLANTATION

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
SJ Tingle ◽  
ER Thompson ◽  
SS Ali ◽  
IK Ibrahim ◽  
E Irwin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Transplantation ◽  
Hospital Stay ◽  
Graft Survival ◽  
Cox Regression ◽  
Risk Groups ◽  
Biliary Complications ◽  
Anastomotic Strictures ◽  
Selection Of Variables ◽  
Independent Risk Factors

Abstract Introduction Biliary leaks and anastomotic strictures are common early biliary complications (EBC) following liver transplantation. However, their impact on outcomes remains controversial and poorly described. Method The NHS registry on adult liver transplantation between 2006 and 2017 was retrospectively reviewed (n=8304). Multiple imputations were performed to account for missing data. Adjusted regression models were used to assess predictors of EBC, and their impact on outcomes. 35 potential variables were included, and backwards stepwise selection enabled unbiased selection of variables for inclusion in final models. Result EBC occurred in 9.6% of patients. Adjusted cox regression revealed that EBCs have a significant and independent impact on graft survival (Leak HR=1.325; P=0.021, Stricture HR=1.514; P=0.002, Leak plus stricture HR=1.533; P=0.034) and patient survival (Leak HR=1.218; P=0.131, Stricture HR=1.578; P&lt;0.001, Leak plus stricture HR=1.507; P=0.044). Patients with EBC had longer median hospital stay (23 versus 15 days; P&lt;0.001) and increased chance for readmission within the first year (56% versus 32%; P&lt;0.001). On adjusted logistic regression the following were identified as independent risk factors for development of EBC: donation following circulatory death (OR=1.280; P=0.009), accessory hepatic artery (OR=1.324; P=0.005), vascular anastomosis time in minutes (OR=1.005; P=0.032) and ethnicity ‘other’ (OR=1.838; P=0.011). Conclusion EBCs prolong hospital stay, increase readmission rates and are independent risk factors for diminished graft survival and increased mortality in liver transplantation. We have identified factors that increase the likelihood of EBC occurrence; further research into interventions to prevent EBCs in these at-risk groups is vital to improve liver transplantation outcomes. Take-home message Using a large registry database we have shown that early anastomotic biliary complications are independent risk factors for decreased graft survival and increased mortality after liver transplantation. Research into interventions to prevent biliary complications in high risk groups are essential to improve liver transplant outcomes.

Mammary-type Myofibroblastoma with Leiomyomatous Differentiation: A Rare Variant with Potential Pitfalls

2021 ◽  
pp. 106689692110313
Author(s):  
Alexander M. Strait ◽  
Julia A. Bridge ◽  
Anthony J. Iafrate ◽  
Marilyn M. Li ◽  
Feng Xu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transcriptome Sequencing ◽  
Smooth Muscle Actin ◽  
The Body ◽  
Muscle Actin ◽  
Mature Adipose Tissue ◽  
Spindle Cells ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Myofibroblastoma is a rare, benign stromal tumor with a diverse morphologic spectrum. Mammary-type myofibroblastoma (MTMF) is the extra-mammary counterpart of this neoplasm and its occurrence throughout the body has become increasingly recognized. Similar morphologic variations of MTMF have now been described which mirror those seen in the breast. We describe a case of intra-abdominal MTMF composed of short fascicles of eosinophilic spindle cells admixed with mature adipose tissue. The spindle cells stained diffusely positive for CD34, desmin, smooth muscle actin, and h-caldesmon by immunohistochemistry. Concurrent loss of RB1 (13q14) and 13q34 loci were confirmed by fluorescence in situ hybridization whereas anchored multiplex PCR and whole transcriptome sequencing did not reveal any pathognomonic fusions suggesting an alternative diagnosis. To the best of our knowledge this is the first documented case of leiomyomatous variant of MTMF.

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