scholarly journals Integrative Analyses of Whole-Transcriptome Sequencing Reveals CeRNA Regulatory Network of mRNAs, lncRNAs, miRNAs and circRNAs in Pulmonary Hypertension Treated with FGF21

2021 ◽  
Author(s):  
Xiuchun Li ◽  
Haijian Cai ◽  
Chi Zhang ◽  
Yaxin Zhang ◽  
Xinghong Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Regulatory Network ◽  
Transcriptome Sequencing ◽  
Epigenetic Modification ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Fibroblast Growth Factor 21 ◽  
Therapeutic Effects ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Abstract Noncoding RNAs have been shown to play important roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNA, miRNA, lncRNA, and circRNA were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Through intersection and predictive analysis, differentially co-expressed mRNA, miRNA, lncRNA, and circRNA were selected, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. A ceRNA regulatory network was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. Then the quantitative real time-PCR validation results were consistent with the results of whole-transcriptome sequencing. This study may provide potential biomarkers, pathway and ceRNA regulatory network in HPH treated with FGF21.

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.

The prognosis of gastric adenocarcinoma depends on the crosstalk between immune profiles and tumor genomic alterations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4035-4035
Author(s):  
Deqiang Wang ◽  
Xiaofeng Chen ◽  
Yaping Xu ◽  
Yuange He ◽  
Lifeng Li ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Transcriptome Sequencing ◽  
Clonal Expansion ◽  
Genomic Alterations ◽  
M1 Macrophages ◽  
Mutual Correlation ◽  
Cell Counts ◽  
M1 Macrophage ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

4035 Background: Gastric adenocarcinoma (GAC) is with a complex microenvironment of tumor cells. A better understanding of the immune landscape of GACs may lead to the improved treatment strategies with ICIs. Methods: To determine whether the molecular characteristics can serve in prognostic stratification of GACs, tumor tissue and blood samples were collected from 231 GAC patients. The median follow-up time was 34 months. The TCR profile was determined by TCR-β CDR3 sequencing while mutation and gene expression profiles were determined by whole exon and whole transcriptome sequencing, respectively. Tumour-infiltrating immune cells were characterized using immunofluorescence (IF) staining. Results: The results showed the OS of patients with high levels of TCR clonality (TCR clonal expansion) was significantly improved compared with patients with low levels (HR = 1.80 and 2.22, p = 0.022 and 0.008, respectively) in the whole group and in the subgroup of patients with stages IB to III disease. Furthermore, low local clonality was an independent risk factor for OS (adjusted-HR = 1.68 and 1.95, p = 0.049 and 0.029, respectively). Thus, TCR clonal expansion in tumour tissue had a strong prognostic value for GAC patients, independent of clinicopathological factors. Based on whole exon and whole transcriptome sequencing, RNF43/FBXW7/ARID2 mutations and local TCR clonality jointly impacted prognosis (p < 0.001), and functional changes in corresponding Wnt pathway/Notch pathway/SWI/SNF complex characterized a GAC subset with enhanced tumour immunogenicity and TCR clonal expansion. TCR CDR3 sequence similarity comparisons yielded clusters of TCR clones of likely similar functions. The most expansive TCR clusters negatively correlated with the percentage of subclonal mutations (Pearson r = -0.8183, p < 0.001), indicating that tumors with less genomic heterogeneity might induce a greater immune response. By IF staining and mutual correlation analysis, only M1 macrophages showed a significant positive correlation with local TCR clonality for epithelia, stroma, and total cell counts. Tumors were categorized according to the density of M1 macrophages, M1 macrophage infiltrated subtype was associated with favorable OS (p = 0.040 and 0.043) and its combination with the local TCR clonality improved prognosis stratification (p < 0.001). Finally, the scoring by local TCR clonality, RNF43/FBXW7/ARID2 mutations and M1 infiltration determined the best prognosis (p < 0.001). Conclusions: TCR profiles were associated with genomic alterations and may serve as a prognostic biomarker for GACs. A multi-omic model including TCR profiles might produce an improved stratification for treatments and outcomes.

Analysis of mRNAs and ncRNAs and Prediction Competing Endogenous RNA Networks in Colorectal Cancer Chemo-Resistance by Whole-Transcriptome Sequencing

2020 ◽  
Author(s):  
Fei Yao ◽  
Chuanren Zhou ◽  
Qiyou Huang ◽  
Xiaoying Huang ◽  
Jie Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Transcriptome Sequencing ◽  
Regulatory Networks ◽  
Parental Cell ◽  
Resistant Cell ◽  
Competing Endogenous Rna ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Abstract Background: Chemo-resistance is a major clinical obstacle to the treatment of colorectal cancer (CRC), mRNAs and non-coding RNAs (ncRNAs) have been reported to modulate the development of chemo-resistance. However, the profiles of mRNAs and ncRNAs as well as competing endogenous RNA (ceRNA) networks in CRC chemo-resistance are still unclear, and whether different drug resistance of CRC have the same mechanisms also needs to be explored. This study aims to uncover the expression of mRNAs and ncRNAs in parental cell lines and different chemo-resistant cell lines, and construct ceRNA regulatory networks by whole-transcriptome sequencing.Methods: The expression of mRNAs and ncRNAs in parental cell lines and drug-resistant cell lines were identified by whole-transcriptome sequencing and bioinformatics methods.Results: A total of 1779 mRNAs, 64 miRNAs, 11 circRNAs and 295 lncRNAs were common differentially expressed in two different chemo-resistant cell lines when compared with the control. In addition, 5,767 lncRNA-miRNA-mRNA relationship pairs and 47 circRNA-miRNA-mRNA pathways were constructed according to ceRNA regulatory rules, in which AC109322.2-hsa-miR-371a-5p-BTNL3 and hsacirc_027876-hsa-miR-582-3p-FREM1 were identified as the most potential ceRNA networks involved in drug resistance to CRC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of two ceRNA regulatory networks showed that the TNF signaling pathway may be crucial in the process of CRC drug resistance.Conclusions: A large number of mRNAs and ncRNAs in chemo-resistant cell lines were different expressed, which may play pivotal roles in development of drug resistance through the ceRNA regulatory network. This study may improve our understanding of the underlying mechanisms and provide a promising therapeutic strategy for CRC chemo-resistance.

scholarly journals Whole-exome and whole-transcriptome sequencing of canine mammary gland tumors

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Ka-Kyung Kim ◽  
Byung-Joon Seung ◽  
Dohyun Kim ◽  
Hee-Myung Park ◽  
Sejoon Lee ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transcriptome Sequencing ◽  
Mammary Gland Tumors ◽  
Whole Exome ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome ◽  
Canine Mammary Gland

Co-culture of functionally enriched cancer stem-like cells and cancer-associated fibroblasts for single-cell whole transcriptome analysis

2019 ◽  
Vol 11 (9) ◽  
pp. 353-361 ◽  
Author(s):  
Yu-Chih Chen ◽  
Seungwon Jung ◽  
Zhixiong Zhang ◽  
Max S Wicha ◽  
Euisik Yoon
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Transcriptome Analysis ◽  
Stromal Cells ◽  
Transcriptome Sequencing ◽  
Functional Enrichment ◽  
Cancer Associated Fibroblasts ◽  
Tumor Initiation ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract Considerable evidence suggests that breast cancer development and metastasis are driven by cancer stem-like cells (CSCs). Due to their unique role in tumor initiation, the interaction between CSCs and stromal cells is especially critical. In this work, we developed a platform to reliably isolate single cells in suspension and grow single-cell-derived spheres for functional enrichment of CSCs. The platform also allows adherent culture of stromal cells for cancer-stromal interaction. As a proof of concept, we grew SUM149 breast cancer cells and successfully formed single-cell-derived spheres. Cancer-associated fibroblasts (CAFs) as stromal cells were found to significantly enhance the formation and growth of cancer spheres, indicating elevated tumor-initiation potential. After on-chip culture for 14 days, we retrieved single-cell derived spheres with and without CAF co-culture for single-cell transcriptome sequencing. Whole transcriptome analysis highlights that CAF co-culture can boost cancer stemness especially ALDHhigh CSCs and alter epithelial/mesenchymal status. Single-cell resolution allows identification of individual CSCs and investigation of cancer cellular heterogeneity. Incorporating whole transcriptome sequencing data with public patient database, we discovered novel genes associated with cancer-CAF interaction and critical to patient survival. The preliminary works demonstrated a reliable platform for enrichment of CSCs and studies of cancer-stromal interaction.

Abstract B93: Gene fusions detected by whole transcriptome sequencing of lung adenocarcinoma.

2011 ◽  
Author(s):  
Takashi Kohno ◽  
Hitoshi Ichikawa ◽  
Yasushi Totoki ◽  
Kazuki Yasuda ◽  
Masaki Hiramoto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Transcriptome Sequencing ◽  
Gene Fusions ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome
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