scholarly journals Construction and prognostic analysis of miRNA-mRNA regulatory network in liver metastasis from colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ruyun Cai ◽  
Qian Lu ◽  
Da Wang
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Immune Cells ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Mesenchymal Transition ◽  
Prognostic Analysis

Abstract Background Colorectal cancer (CRC) is one of the most common cancers in the world, and liver metastasis is the leading cause of colorectal cancer-related deaths. However, the mechanism of liver metastasis in CRC has not been clearly elucidated. Methods Three datasets from the Gene Expression Omnibus (GEO) database were analyzed to obtain differentially expressed genes (DEGs), which were subjected to functional enrichment analysis and protein-protein interaction analysis. Subsequently, mRNA-miRNA network was constructed, and the associated DEGs and DEMs were performed for prognostic analysis. Finally, we did infiltration analysis of growth arrest specific 1 (GAS1)-associated immune cells. Results We obtained 325 DEGs and 9 differentially expressed miRNAs (DEMs) between primary CRC and liver metastases. Enrichment analysis and protein-protein interactions (PPI) further revealed the involvement of DEGs in the formation of the inflammatory microenvironment and epithelial-mesenchymal transition (EMT) during the liver metastases process in CRC. Survival analysis demonstrated that low-expressed GAS1 as well as low-expressed hsa-miR-33b-5p was a favorable prognostic indicator of overall survival. Further exploration of GAS1 revealed that its expression was interrelated with the infiltration of immune cells in tumor tissues. Conclusions In summary, DEGs, DEMs, and their interactions found in liver metastasis of CRC may provide a basis for further understanding of the mechanism of CRC metastasis.

scholarly journals Construction and Prognostic Analysis of miRNA-mRNA Regulatory Network in Liver Metastasis from Colorectal Cancer

2020 ◽  
Author(s):  
Ruyun Cai ◽  
Qian Lu ◽  
Da Wang
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Immune Cells ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Mesenchymal Transition ◽  
Prognostic Analysis

Abstract Background: Colorectal cancer (CRC) is one of the most common cancers in the world, and liver metastasis is the leading cause of colorectal cancer-related deaths. However, the mechanism of liver metastasis in CRC hasn’t been clearly elucidated.Methods: Three datasets from the Gene Expression Omnibus (GEO) database were analyzed to obtain differentially expressed genes (DEGs), which were subjected to functional enrichment analysis and protein-protein interaction analysis. Subsequently, mRNA-miRNA network was constructed and the associated DEGs and DEMs were performed for prognostic analysis. Finally, we did infiltration analysis of GAS1-associated immune cells. Results: We obtained 325 DEGs and 9 differentially expressed miRNAs (DEMs) between primary CRC and liver metastases. Enrichment analysis and protein-protein interactions (PPI) further revealed the involvement of DEGs in the formation of the inflammatory microenvironment and epithelial-mesenchymal transition (EMT) during the liver metastases process in CRC. Survival analysis demonstrated that low-expressed GAS1 as well as low-expressed hsa-miR-33b-5p was a favorable prognostic indicator of overall survival. Further exploration of GAS1 revealed that its expression was interrelated with the infiltration of immune cells in tumor tissues. Conclusions: In summary, DEGs, DEMs and their interactions found in liver metastasis of CRC may provide a basis for further understanding of the mechanism of CRC metastasis.

scholarly journals The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

2018 ◽  
Vol 19 (12) ◽  
pp. 3711 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Cancer Progression ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Cancer Management ◽  
Incidence And Mortality ◽  
The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

scholarly journals SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Hao Wang ◽  
Jinwen Yin ◽  
Yuntian Hong ◽  
Anli Ren ◽  
Haizhou Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Macrophage Polarization ◽  
Clinical Stage ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Secretory Proteins ◽  
Advanced Clinical Stage ◽  
Multiple Tumor ◽  
Immune Infiltration

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

scholarly journals Genomics and prognosis analysis of epithelial-mesenchymal transition in colorectal cancer patients

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zizhen Zhang ◽  
Sheng Zheng ◽  
Yifeng Lin ◽  
Jiawei Sun ◽  
Ning Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Related Gene ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Abstract Background The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for chemoresistance in colorectal cancer (CRC). The aim of this research is to develop an EMT-based prognostic signature in CRC. Methods RNA-seq and microarray data, together with clinical information, were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A total of 244 differentially expressed EMT-related genes (ERGs) were obtained by comparing the expression between normal and tumor tissues. An EMT-related signature of 11 genes was identified as crucially related to the overall survival (OS) of patients through univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and Cox regression analysis. Finally, we established a clinical nomogram to predict the survival possibility of CRC patients by integrating clinical characteristics and the EMT-related gene signature. Results Two hundred and forty-four differentially expressed ERGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that EMT-related signaling pathway genes were highly related to CRC. Kaplan-Meier analysis revealed that the 11-EMT signature could significantly distinguish high- and low-risk patients in both TCGA and GEO CRC cohorts. In addition, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusion We developed a novel EMT-related gene signature for the prognosis prediction of CRC patients, which could improve the individualized outcome prediction in CRC.

scholarly journals Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhao Hui ◽  
Wang Zhanwei ◽  
Yang Xi ◽  
Liu Jin ◽  
Zhuang Jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Interactions ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Normal Tissues ◽  
Cerna Network ◽  
Cancer Tissues

Objective. To screen some RNAs that correlated with colorectal cancer (CRC). Methods. Differentially expressed miRNAs, lncRNAs, and mRNAs between cancer tissues and normal tissues in CRC were identified using data from the Gene Expression Omnibus (GEO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interactions (PPIs) were performed to do the functional enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed which correlated with CRC. RNAs in this network were subjected to analyze the relationship with the patient prognosis. Results. A total of 688, 241, and 103 differentially expressed genes (diff-mRNA), diff-lncRNA, and diff-miRNA were obtained between cancer tissues and normal tissues. A total of 315 edges were obtained in the ceRNA network. lncRNA RP11-108K3.2 and mRNA ONECUT2 correlated with prognosis. Conclusion. The identified RNAs and constructed ceRNA network could provide great sources for the researches of therapy of the CRC. And the lncRNA RP11-108K3.2 and mRNA ONECUT2 may serve as a novel prognostic predictor of CRC.

scholarly journals Identification and Interaction Analysis of Significant Genes and MicroRNAs in Pterygium

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Siying He ◽  
Hui Sun ◽  
Yifang Huang ◽  
Shiqi Dong ◽  
Chen Qiao ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas

Purpose. MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms. Methods. MiRNA expression was initially extracted and pooled by published literature. Microarray data about differentially expressed genes was downloaded from Gene Expression Omnibus (GEO) database and analyzed with the R programming language. Functional and pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network was constructed with the STRING database. The associations between chemicals, differentially expressed miRNAs, and differentially expressed genes were predicted using the online resource. All the networks were constructed using Cytoscape. Results. We found that 35 miRNAs and 301 genes were significantly differentially expressed. Functional enrichment analysis showed that upregulated genes were significantly enriched in extracellular matrix (ECM) organization, while downregulated genes were mainly involved in cell death and apoptotic process. Finally, we concluded the chemical-gene affected network, miRNA-mRNA interacted networks, and significant pathway network. Conclusion. We identified lists of differentially expressed miRNAs and genes and their possible interaction in pterygium. The networks indicated that ECM breakdown and EMT might be two major pathophysiological mechanisms and showed the potential significance of PI3K-Akt signalling pathway. MiR-29b-3p and collagen family (COL4A1 and COL3A1) might be new treatment target in pterygium.

scholarly journals The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

2018 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Beta Catenin ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Cancer Management ◽  
Incidence And Mortality ◽  
The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis, published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial-mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.  

scholarly journals Systematic Profiling of Diagnostic and Prognostic Value of Autophagy-Related Genes for Sarcoma Patients

2020 ◽  
Author(s):  
Yuanhe Wang ◽  
Jianyi Li ◽  
Cheng Shao ◽  
Xiaojie Tang ◽  
Yukun Du ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Disease Free Survival ◽  
Independent Set ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
Systematic Analysis

Abstract Background: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking.Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results: In total, 84 DEIRGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between twp clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.636 for the OS and DFS nomograms, respectively.Conclusion: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

scholarly journals The IRF family can influence tumor immunity and the prognosis of patients with colorectal cancer

2021 ◽  
Author(s):  
Yan-Jie Chen ◽  
Shu-Neng Luo ◽  
Ling Dong ◽  
Tao-Tao Liu ◽  
Xi-Zhong Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Immune Cells ◽  
Tumor Stroma ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Validation Dataset ◽  
Expression Data ◽  
Tumor Tissues ◽  
Patient Prognosis

Abstract Background: The roles of interferon-regulatory factors (IRFs) in colorectal cancer (CRC) have not been studied through bioinformatics analysis. Methods: We used gene- and microRNA-expression data for patients with somatic mutations and colon adenocarcinoma/rectum adenocarcinoma from The Cancer Genome Atlas Genomic Data Commons as a training dataset. Gene-expression data (accessions GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus database as the validation dataset. Expressional differences, clinical correlations, disease prognosis, functional enrichment, and immune correlations of IRF genes were analyzed. The results were validated via immunohistochemistry. Results: The mRNA-expression levels of IRF3 and IRF7 differed between tumor and normal tissues and were correlated with patient prognosis. The IRF score was an independent risk factor for overall survival. IRFs recruited inflammatory cells; however, the immune and stromal scores showed inflammatory-cell recruitment only in the tumor stroma; therefore, they did not help eliminate tumor cells. Functional-enrichment analysis and pan-cancer expression analysis revealed that IRFs were differentially expressed in tumor tissues and associated with patient prognosis. Conclusions: IRFs were differentially expressed in tumor tissues and were associated with prognosis in CRC patients. Although IRFs can promote the infiltration of immune cells, the immune and stromal score showed that the infiltrated immune cells mostly stayed in the tumor stroma and cannot directly eliminate the tumor. Our findings can help to improve CRC prognosis and treatment strategies.

scholarly journals An Integrative Omics Approach Reveals Involvement of BRCA1 in Hepatic Metastatic Progression of Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2380
Author(s):  
Daniela Gerovska ◽  
Gorka Larrinaga ◽  
Jon Danel Solano-Iturri ◽  
Joana Márquez ◽  
Patricia García Gallastegi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Liver Metastasis ◽  
Protein Expression ◽  
Liver Metastases ◽  
Liver Cells ◽  
Differentially Expressed ◽  
Sinusoidal Endothelial Cells ◽  
Ito Cells ◽  
Brca1 Protein

(1) Background & Aims: The roles of different cells in the tumor microenvironment (TME) are critical to the metastatic process. The phenotypic transformation of the liver cells is one of the most important stages of the hepatic metastasis progression of colorectal cancer (CRC). Our aim was to identify the major molecules (i.e., genes, miRNAs and proteins) involved in this process. (2) Methods: We isolated and performed whole-genome analysis of gene, miRNA, and protein expression in three types of liver cells (Ito cells, Kupffer cells, and liver sinusoidal endothelial cells) from the TME of a murine model of CRC liver metastasis. We selected the statistically significant differentially expressed molecules using the Student’s t-test with Benjamini-Hochberg correction and performed functional statistically-significant enrichment analysis of differentially expressed molecules with hypergeometric distribution using the curated collection of molecular signatures, MSigDB. To build a gene-miRNA-protein network centered in Brca1, we developed a software package (miRDiana) that collects miRNA targets from the union of the TargetScan, MicroCosm, mirTarBase, and miRWalk databases. This was used to search for miRNAs targeting Brca1. We validated the most relevant miRNAs with real-time quantitative PCR. To investigate BRCA1 protein expression, we built tissue microarrays (TMAs) from hepatic metastases of 34 CRC patients. (3) Results: Using integrated omics analyses, we observed that the Brca1 gene is among the twenty transcripts simultaneously up-regulated in all three types of TME liver cells during metastasis. Further analysis revealed that Brca1 is the last BRCA1-associated genome surveillance complex (BASC) gene activated in the TME. We confirmed this finding in human reanalyzing transcriptomics datasets from 184 patients from non-tumor colorectal tissue, primary colorectal tumor and colorectal liver metastasis of the GEO database. We found that the most probable sequence of cell activation during metastasis is Endothelial→Ito→Kupffer. Immunohistochemical analysis of human liver metastases showed the BRCA1 protein was co-localized in Ito, Kupffer, and endothelial cells in 81.8% of early or synchronous metastases. However, in the greater part of the metachronous liver metastases, this protein was not expressed in any of these TME cells. (4) Conclusions: These results suggest a possible role of the co-expression of BRCA1 in Ito, Kupffer, and sinusoidal endothelial cells in the early occurrence of CRC liver metastases, and point to BRCA1 as a potential TME biomarker.

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