scholarly journals Network Pharmacology-based Elucidation of Molecular Biological Mechanisms of Kanglaite Injection for Treatment of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Author(s):  
Bowen Xu ◽  
Wenchao Dan ◽  
Jie Lj ◽  
Xiaoxiao Zhang ◽  
Luchang Cao ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Drug Targets ◽  
Differentially Expressed ◽  
Ductal Adenocarcinoma ◽  
Network Pharmacology ◽  
Biological Mechanisms ◽  
Pathway Network ◽  
Gene Pathway

Abstract Background: Kanglaite injection (KLTi) has shown good clinical efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, its molecular biological mechanisms are still unclear. This study used network pharmacology approach to investigate the molecular biological mechanisms of KLTi.Methods: Compounds in KLTi were screened using TCMSP and drug targets were obtained from the DRUGBANK. Next, the GEO database was searched for differentially expressed genes in cancerous tissues and healthy tissues of PDAC patients to identify targets. Subsequently, the protein-protein interaction data of KLTi and PDAC targets were constructed by BisoGenet. A visual analysis was done to extract KLTi candidate genes for PDAC. The candidate genes were enriched using GO and KEGG by Metascape, and the gene-pathway network was constructed to further screen the key genes.Results: A total of 10 active compounds and 36 drug targets were screened for KLTi, 919 differentially expressed genes associated with PDAC were identified from GEO, and 139 KLTi candidate genes against PDAC were excavated by BisoGenet. The gene-pathway network showed RELA, NFKB1, IKBKG, JUN, MAPK1, TP53, and AKT1 as the core genes, predicting that KLTi intervenes in PDAC by acting on these genes.Conclusions: Our study suggested that KLTi plays an anti-PDAC role by intervening in the cell cycle, inducing apoptosis, regulating protein binding, inhibiting nerve invasion, and down-regulating the NF-κB, MAPK, and PI3K-Akt signaling pathways. In addition, it might also directly participate in the pancreatic cancer pathway. These results provide new evidence and therapeutic direction for subsequent clinical applications and basic research on KLTi in PDAC.

scholarly journals Autophagy Regulatory Genes MET and RIPK2 Play a Prognostic Role in Pancreatic Ductal Adenocarcinoma: A Bioinformatic Analysis Based on GEO and TCGA

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xingyu Li ◽  
Zhiqiang Li ◽  
Hongwei Zhu ◽  
Xiao Yu
Keyword(s):  
Single Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Differentially Expressed Genes ◽  
Clinical Application ◽  
Regulatory Genes ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Ductal Adenocarcinoma ◽  
Rna Seq

Pancreatic ductal adenocarcinoma is a common malignant tumor with a poor prognosis. Autophagy activity changes in both cancer cells and microenvironment and affects the progression of pancreatic ductal adenocarcinoma. The purpose of this study was to predict the prognostic autophagy regulatory genes and their role in the regulation of autophagy in pancreatic ductal adenocarcinoma. We draw conclusions based on gene expression data from different platforms: GSE62165 and GSE85916 from the array platform, TCGA from the bulk RNA-seq platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differentially expressed genes in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue based on GSE62165. Then, we screened prognostic genes based on GSE85916 and TCGA. Furthermore, we constructed a risk signature composed of the prognostic differentially expressed genes. Finally, we predicted the probable role of these genes in regulating autophagy and the types of cell expressing these genes. According to our screening criteria, there were only two genes: MET and RIPK2, selected into the development of the risk signature. However, evaluated by log-rank tests, receiver operating characteristic curves, and calibration curves, the risk signature was worth considering its clinical application because of good sensitivity, specificity, and stability. Besides, we predicted that both MET and RIPK2 promote autophagy in pancreatic ductal adenocarcinoma by gene set enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET and RIPK2 were expressed in cancer cells while RIPK2 was also expressed in monocytes and neutrophils. After comprehensive analysis, we found that both MET and RIPK2 are related to the prognosis of pancreatic ductal adenocarcinoma and provided some associated clues for clinical application and basic experiment research.

Immune-related genes LAMA2 and IL1R1 correlate with tumor sites and predict poor survival in pancreatic adenocarcinoma

2021 ◽  
Author(s):  
Mengna Zhang ◽  
Lirong Zeng ◽  
Yanan Peng ◽  
Bin Fan ◽  
PengFei Chen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Pancreatic Head ◽  
Differentially Expressed ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Head Cancer ◽  
Pancreatic Head Cancer ◽  
Gene Sets ◽  
Immune Related Genes

Aims: The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. Methods: The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. Results: IL1R1 and LAMA2 were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. Conclusion: The authors identified IL1R1 and LAMA2 as immune- and locus-associated genes, and their high expression predicted a poor prognosis.

Pathogenic Genes Selection Model of Genetic Disease based on Network Motifs Slicing Feedback

2019 ◽  
Vol 16 (5) ◽  
pp. 392-401
Author(s):  
Shengli Zhang ◽  
Zekun Tong ◽  
Haoyu Yin ◽  
Yifan Feng
Keyword(s):  
Genetic Disease ◽  
Drug Targets ◽  
Selection Model ◽  
Network Motifs ◽  
Gene Set ◽  
Pathway Network ◽  
Gene Pathway ◽  
Pathogenic Genes ◽  
Pathogenic Gene ◽  
Selection Of

Background: Finding the pathogenic gene is very important for understanding the pathogenesis of the disease, locating effective drug targets and improving the clinical level of medical treatment. However, the existing methods for finding the pathogenic genes still have limitations, for instance the computational complexity is high, and the combination of multiple genes and pathways has not been considered to search for highly related pathogenic genes and so on. Methods: We propose a pathogenic genes selection model of genetic disease based on Network Motifs Slicing Feedback (NMSF). We find a point set which makes the conductivity of the motif minimum then use it to substitute for the original gene pathway network. Based on the NMSF, we propose a new pathogenic genes selection model to expand pathogenic gene set. Results: According to the gene set we have obtained, selection of key genes will be more accurate and convincing. Finally, we use our model to screen the pathogenic genes and key pathways of liver cancer and lung cancer, and compare the results with the existing methods. Conclusion: The main contribution is to provide a method called NMSF which simplifies the gene pathway network to make the selection of pathogenic gene simple and feasible. The fact shows our result has a wide coverage and high accuracy and our model has good expeditiousness and robustness.

scholarly journals Identifying Candidate Genes for Hypoxia Adaptation of Tibet Chicken Embryos by Selection Signature Analyses and RNA Sequencing

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 823
Author(s):  
Xiayi Liu ◽  
Xiaochen Wang ◽  
Jing Liu ◽  
Xiangyu Wang ◽  
Haigang Bao
Keyword(s):  
Candidate Genes ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Gallus Gallus ◽  
Differentially Expressed ◽  
Tibet Plateau ◽  
Embryonic Liver ◽  
Selection Signature ◽  
Chicken Embryos ◽  
Hypoxia Adaptation

The Tibet chicken (Gallus gallus) lives on the Qinghai–Tibet Plateau and adapts to the hypoxic environment very well. The objectives of this study was to obtain candidate genes associated with hypoxia adaptation in the Tibet chicken embryos. In the present study, we used the fixation index (Fst) and cross population extended haplotype homozygosity (XPEHH) statistical methods to detect signatures of positive selection of the Tibet chicken, and analyzed the RNA sequencing data from the embryonic liver and heart with HISAT, StringTie and Ballgown for differentially expressed genes between the Tibet chicken and White leghorn (Gallus gallus, a kind of lowland chicken) embryos hatched under hypoxia condition. Genes which were screened out by both selection signature analysis and RNA sequencing analysis could be regarded as candidate genes for hypoxia adaptation of chicken embryos. We screened out 1772 genes by XPEHH and 601 genes by Fst, and obtained 384 and 353 differentially expressed genes in embryonic liver and heart, respectively. Among these genes, 89 genes were considered as candidate genes for hypoxia adaptation in chicken embryos. ARNT, AHR, GSTK1 and FGFR1 could be considered the most important candidate genes. Our findings provide references to elucidate the molecular mechanism of hypoxia adaptation in Tibet chicken embryos.

scholarly journals Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats

2018 ◽  
Vol 50 (2) ◽  
pp. 668-678 ◽  
Author(s):  
Wen-Qian Zhang ◽  
Miao Zhao ◽  
Ming-Yu Huang ◽  
Ji-Long Liu
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Differentially Expressed ◽  
Rat Uterus ◽  
Mouse Uterus ◽  
Pathway Network ◽  
Implantation Sites ◽  
High Selection ◽  
Transcriptomic Changes

Background/Aims: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. Methods: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. Results: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. Conclusion: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.

MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma

2015 ◽  
Vol 42 (10) ◽  
pp. 563-577 ◽  
Author(s):  
Longhao Sun ◽  
Corrine Ying Xuan Chua ◽  
Weijun Tian ◽  
Zhixiang Zhang ◽  
Paul J. Chiao ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Ductal Adenocarcinoma ◽  
Pathway Network

scholarly journals Differentially expressed genes in preimplantation human embryos: potential candidate genes for blastocyst formation and implantation

2016 ◽  
Vol 33 (8) ◽  
pp. 1017-1025 ◽  
Author(s):  
Erika M. Munch ◽  
Amy E. Sparks ◽  
Jesus Gonzalez Bosquet ◽  
Lane K. Christenson ◽  
Eric J. Devor ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Human Embryos ◽  
Potential Candidate ◽  
Blastocyst Formation

scholarly journals Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia

2019 ◽  
Author(s):  
Leah J Radeke ◽  
Michael Herman
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Stenotrophomonas Maltophilia ◽  
Defense Mechanisms ◽  
Virulent Strain ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Transcriptomic Response ◽  
C Elegans ◽  
Realistic Interaction

Abstract Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

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