scholarly journals Identification of Key Genes and Prognostic Analysis between Chromophobe Renal Cell Carcinoma and Renal Oncocytoma by Bioinformatic Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Hongwei Wu ◽  
Lijing Fan ◽  
Haiping Liu ◽  
Baozhang Guan ◽  
Bo Hu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Renal Oncocytoma ◽  
Receptor Signaling ◽  
Kaplan Meier ◽  
Receptor Signaling Pathway ◽  
Key Genes ◽  
Cell Receptor Signaling

The present techniques of clinical and histopathological diagnosis hardly distinguish chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO). To identify differentially expressed genes (DEGs) as effective biomarkers for diagnosis and prognosis of ChRCC and RO, three mRNA microarray datasets (GSE12090, GSE19982, and GSE8271) were downloaded from the GEO database. Functional enrichment analysis of DEGs was performed by DAVID. STRING and Cytoscape were applied to construct the protein-protein interaction (PPI) network and key modules of DEGs. Visualized plots were conducted by the R language. We downloaded clinical data from the TCGA database and the influence of key genes on the overall survival of ChRCC was performed by Kaplan–Meier and Cox analyses. Gene set enrichment analysis (GSEA) was utilized in exploring the function of key genes. A total of 79 DEGs were identified. Enrichment analyses revealed that the DEGs are closely related to tissue invasion and metastasis of cancer. Subsequently, 14 hub genes including ESRP1, AP1M2, CLDN4, and CLDN7 were detected. Kaplan–Meier analysis indicated that the low expression of CLDN7 and GNAS was related to the worse overall survival in patients with ChRCC. Univariate Cox analysis showed that CLDN7 might be a helpful biomarker for ChRCC prognosis. Subgroup analysis revealed that the expression of CLDN7 showed a downtrend with the development of the clinical stage, topography, and distant metastasis of ChRCC. GSEA analysis identified that cell adhesion molecules cams, B cell receptor signaling pathway, T cell receptor signaling pathway, RIG-I like receptor signaling pathway, Toll-like receptor signaling pathway, and apoptosis pathway were associated with the expression of CLDN7. In conclusion, ESRP1, AP1M2, CLDN4, PRSS8, and CLDN7 were found to distinguish ChRCC from RO. Besides, the low expression of CLDN7 was closely related to ChRCC progression and could serve as an independent risk factor for the overall survival in patients with ChRCC.

scholarly journals Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Chun-long Zheng ◽  
Qiang Lu ◽  
Nian Zhang ◽  
Peng-yu Jing ◽  
Ji-peng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Risk Scores ◽  
Pathway Enrichment Analysis ◽  
Receptor Signaling ◽  
Immune Infiltration ◽  
Receptor Signaling Pathway

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.

scholarly journals The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway

Immunity ◽  
2007 ◽  
Vol 26 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Marzenna Blonska ◽  
Bhanu P. Pappu ◽  
Reiko Matsumoto ◽  
Hongxiu Li ◽  
Bing Su ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Signaling Complex ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

An HSP90 Inhibitor, PU-H71, Antagonizes Stroma-Induced Pro-Survival Effects in CLL through Its Inhibition of Multi-Component B-Cell Receptor Signaling Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5289-5289
Author(s):  
Ailin Guo ◽  
Pin Lu ◽  
Chaojie Zhen ◽  
Gabriela Chiosis ◽  
Yue Lynn Wang
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Hsp90 Inhibitor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Bcr Signaling ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

Abstract Background: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B-cells in the hematopoietic system. The B-cell receptor (BCR) plays an essential role in the pathogenesis of CLL and many components of the BCR signaling pathway are known clients of HSP90. HSP90 is a highly conserved molecular chaperone that ensures the proper folding and stabilization of its client proteins. In this study, we investigated whether PU-H71 a novel purine-scaffold HSP90 Inhibitor, has anti-tumor activity in CLL by destabilizing BCR signaling pathway constituents. Design: Fresh CLL cells were isolated and cultured ex vivo with or without stromal co-culture. Molecular and cellular events were studied in PU-H71-treated and control CLL cells. Results: Immunoblotting revealed that a significantly higher amount of HSP90 is present in CLL cells than in peripheral blood mononuclear cells (PBMC), suggesting the chaperone is pathogenically relevant. We found that PU-H71 caused the death of CLL cells in a dose and time dependent manner while the viability of either PBMC or normal B lymphocytes were not affected. PU-H71 induced apoptosis resulting in CLL cell death as it caused mitochondrial cytochrome C release and a decrease in the abundance of several anti-apoptotic proteins. Interestingly, PU-H71 has the ability to counteract the pro-survival effects of the stroma and caused apoptosis in CLL cells co-cultured with stroma. To gain mechanistic insights into how PU-H71 acts, we examined the BCR signaling pathway. We found that the amounts of several key components of the pathway were reduced by PU-H71 treatment. This occurred even in the presence of stromal co-culture. The results suggest that PU-H71 antagonizes the function of HSP90 leading to the destabilization of the BCR signaling transducers. A chemical pull-down experiment revealed the co-existence of the BCR components and HSP90 in the same complex, suggesting these BCR constituents are indeed clients of HSP90 in CLL cells. Further, specific genetic knock-down of the signal transducers by siRNA confirmed their key roles in mediating the survival of CLL cells. Conclusions: PU-H71 antagonizes stroma-induced pro-survival effects in CLL through its inhibition of the B-cell receptor signaling pathway. Our results suggest that PU-H71 may serve as a useful therapy against CLL and is worth further clinical development. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of potential microRNAs and KEGG pathways in denervation muscle atrophy based on meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinyi Gu ◽  
Bo Jin ◽  
Zhidan Qi ◽  
Xiaofeng Yin
Keyword(s):  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Meta Analysis ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Signaling ◽  
Denervated Muscle ◽  
Kegg Pathways ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

AbstractThe molecular mechanism of muscle atrophy has been studied a lot, but there is no comprehensive analysis focusing on the denervated muscle atrophy. The gene network that controls the development of denervated muscle atrophy needs further elucidation. We examined differentially expressed genes (DEGs) from five denervated muscle atrophy microarray datasets and predicted microRNAs that target these DEGs. We also included the differentially expressed microRNAs datasets of denervated muscle atrophy in previous studies as background information to identify potential key microRNAs. Finally, we compared denervated muscle atrophy with disuse muscle atrophy caused by other reasons, and obtained the Den-genes which only differentially expressed in denervated muscle atrophy. In this meta-analysis, we obtained 429 up-regulated genes, 525 down-regulated genes and a batch of key microRNAs in denervated muscle atrophy. We found eight important microRNA-mRNA interactions (miR-1/Jun, miR-1/Vegfa, miR-497/Vegfa, miR-23a/Vegfa, miR-206/Vegfa, miR-497/Suclg1, miR-27a/Suclg1, miR-27a/Mapk14). The top five KEGG pathways enriched by Den-genes are Insulin signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and B cell receptor signaling pathway. Our research has delineated the RNA regulatory network of denervated muscle atrophy, and uncovered the specific genes and terms in denervated muscle atrophy.

scholarly journals Screening for differentially expressed circRNAs in ischemic stroke by RNA sequencing

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Duncan Wei ◽  
Jian Chen ◽  
Xiaopu Chen ◽  
Shaoyan Wu ◽  
Zhaolin Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Signaling ◽  
Qrt Pcr ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling ◽  
Host Genes

Abstract Background Ischemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke. Methods RNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Results A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. Conclusions The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

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