scholarly journals Combined Analysis of the Aberrant Epigenetic Alteration of Colorectal Cancer

2020 ◽  
Author(s):  
Xiao-liang Xing ◽  
Zhi-Yong Yao ◽  
Ti Zhang ◽  
Ning Zhu ◽  
Xingyu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Adenocarcinoma ◽  
Differential Methylation ◽  
The Cancer Genome Atlas ◽  
The Third ◽  
Common Cancer ◽  
Differential Expression Genes ◽  
Cancer Genome Atlas ◽  
Genome Atlas ◽  
Potential Biomarkers

Abstract BackgroundColorectal cancer (CRC) is the third most common cancer which could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) mainly. Accumulating evidence indicatedmethylations are involved in multiple tumors.MethodsTo know the effect of abnormal methylation in COAD, READ and CRC, we downloaded methylation and mRNA data of COAD and READ from The Cancer Genome Atlas (TCGA) database. And then, we used DESeq2, ChAMP, DAVID 6.8, Cytoscape_3.7.2 and Correlation analysis to identify the potential biomarkers.ResultsWe obtain 12 potential biomarkers (APBB1, CDC42SE2, EIF4E3, FBXO17, FES, GNPNAT1, HSPA1A, OSBPL3, RORC, SALL1, SPEG, and TCF7L1) directly associated with the pathologic TNM of COAD maybe regulated by 28 differential methylations; 2 potential biomarkers (AQP1 and HOXA3) directly associated with pathologic NM maybe regulated by 8 differential methylations; and 15 potential biomarkers (ADAMTSL3, ANXA9, APBB1, AQP1, C2CD4A, CLIP3, DNAJC15, EIF4E3, FAM160A1, GNG4, HLX, HSPA1A, LAYN, NR3C2, and SYT1)directly associated with the pathologic TNM of COAD maybe regulated by 29 differential methylations. Furthermore, weconstruct the network of differential methylation and differential expression genes. In addition, we also obtain 1 methylation (cg18149207), 2 methylations (cg02000808 and cg21134232) and 2 methylations (cg04408595 and cg19413725) associated with the overall survival.ConclusionOur results provide an analysis of theoretical knowledge and clinical outcomes, but more researches are needed to confirm our findings.

scholarly journals MicroRNA-Related Prognosis Biomarkers from High-Throughput Sequencing Data of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Ti Zhang ◽  
Ning Zhu ◽  
Yuan-Wu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Differential Expression ◽  
High Throughput Sequencing ◽  
Survival Rates ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Differential Expression Genes ◽  
Cancer Genome Atlas

Background. Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors. Methods. In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers. Results. We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly. Conclusion. In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.

scholarly journals Editing and Expression of miR-589-5p as an Important Biomarker in Colorectal Cancer

2020 ◽  
Author(s):  
Yuanyi Yue ◽  
Qiang Zhang ◽  
Li Xiao
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Expression Levels ◽  
The Third ◽  
Common Cancer ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Mirna Editing ◽  
Editing Level

Abstract Objectives: Colorectal cancer (CRC) is recognized as the third most common cancer worldwide. Recently, emerging evidence showed that microRNA (miRNA) A-to-I editing plays crucial roles in cancer prognosis as well as cancer therapy. However, the relationship between CRC and miRNA editing remains not fully understood. Herein, we presented the first comprehensive analysis of miRNA editing events in CRC. Methods: Using patient data from The Cancer Genome Atlas (TCGA), we performed editing events and detected the expression levels of miR-589-5p. Results: we identified both editing events and the expression levels of miR-589-5p are significantly associated with Consensus Molecular Subtyping (CMS), especially for CMS4. The editing and expression levels of miR-589-5p impact almost completely different sets of gene expression, indicating the edited miR-589-5p plays a different role in CRC progression, compared to the wildtype miR-589-5p. Conclusions: In conclusion, our study provided the first association of miRNA editing and CRC. We demonstrated that expression and editing level of miR‑589‑5p may work as a novel biomarker for both prognosis and diagnosis in CRC.

scholarly journals Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Somatic Mutation ◽  
Mutation Rate ◽  
Germ Line ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

scholarly journals Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets

2017 ◽  
Vol 41 (4) ◽  
pp. 1468-1480 ◽  
Author(s):  
Yingjie Shao ◽  
Wendong Gu ◽  
Zhonghua Ning ◽  
Xing Song ◽  
Honglei Pei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Esophageal Cancer ◽  
Solid Tumors ◽  
Prognostic Value ◽  
Meta Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. Methods: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. Results:33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn’t predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. Conclusion: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

scholarly journals Diagnosis and prognostic value of C-X-C motif chemokine ligand 1 in colon adenocarcinoma based on The Cancer Genome Atlas and Guangxi cohort

2021 ◽  
Vol 12 (18) ◽  
pp. 5506-5518
Author(s):  
Yi-Zhen Gong ◽  
Hui Ma ◽  
Guo-Tian Ruan ◽  
Li-Chen Zhu ◽  
Xi-Wen Liao ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Colon Adenocarcinoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Chemokine Ligand ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Identification of intestinal flora-related key genes and therapeutic drugs in colorectal cancer

2020 ◽  
Author(s):  
Jiayu Zhang ◽  
Huaiyu Zhang ◽  
Faping Li ◽  
Zheyu Song ◽  
Yezhou Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Flora ◽  
Interaction Network ◽  
Gene Interaction ◽  
The Cancer Genome Atlas ◽  
Interaction Database ◽  
Therapeutic Drugs ◽  
Cancer Genome Atlas ◽  
Key Genes ◽  
Genome Atlas

Abstract Background: Colorectal cancer (CRC) is a multifactorial tumor and a leading cause of cancer-specific deaths worldwide. Recent research has shown that the alteration of intestinal flora contributes to the development of CRC. However, the molecular mechanism by which intestinal flora influences the pathogenesis of CRC remains unclear. This study aims to explore the key genes underlying the effect of intestinal flora on CRC and therapeutic drugs for CRC.Methods: Intestinal flora-related genes were determined using text mining. Based on The Cancer Genome Atlas database, differentially expressed genes (DEGs) between CRC and normal samples were identified with the limma package of the R software. Then, the intersection of the two gene sets was selected for enrichment analyses using the tool Database for Annotation, Visualization and Integrated Discovery. Protein interaction network analysis was performed for identifying the key genes using STRING and Cytoscape. The correlation of the key genes with overall survival of CRC patients was analyzed. Finally, the key genes were queried against the Drug-Gene Interaction database to find drug candidates for treating CRC.Results: 518 genes associated with intestinal flora were determined by text mining. Based on The Cancer Genome Atlas database, we identified 48 DEGs associated with intestinal flora, including 25 up-regulated and 23 down-regulated DEGs in CRC. The enrichment analyses indicated that the selected genes were mainly involved in cell-cell signaling, immune response, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. The protein-protein interaction network was constructed with 13 nodes and 35 edges. Moreover, 8 genes in the significant cluster were considered as the key genes and chemokine (C-X-C motif) ligand 8 (CXCL8) correlated positively with the overall survival of CRC patients. Finally, a total of 24 drugs were predicted as possible drugs for CRC treatment using the Drug-Gene Interaction database.Conclusions: These findings of this study may provide new insights into CRC pathogenesis and treatments. The prediction of drug-gene interaction is of great practical significance for exploring new drugs or novel targets for existing drugs.

scholarly journals miR-330 Regulates Colorectal Cancer Oncogenesis by Targeting BACH1

2020 ◽  
Vol 10 (3) ◽  
pp. 444-451
Author(s):  
Solmaz Shirjang ◽  
Behzad Mansoori ◽  
Ali Mohammadi ◽  
Neda Shajari ◽  
Pascal H.G. Duijf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Oncogenic Signaling ◽  
Patients With Cancer ◽  
Colon And Rectal Cancer ◽  
Cancer Genome Atlas ◽  
Endothelial Growth Factor

Purpose : Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330. Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting. Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to the COAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR330-5p were reduced in CRC tumors compared to normal controls. The miR-330 induction prevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-C chemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR) proteins expressions. Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells. The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression in posttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330 could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenic signaling pathway.

scholarly journals MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Melania Scarpa ◽  
Cesare Ruffolo ◽  
Andromachi Kotsafti ◽  
Fabio Canal ◽  
Francesca Erroi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Sporadic Colorectal Cancer ◽  
Tlr4 Expression ◽  
Mmr Genes ◽  
Favorable Prognosis ◽  
Cancer Genome Atlas ◽  
Myd88 Signaling ◽  
Genome Atlas

Patients with mismatch repair (MMR)-deficient colorectal cancer (CRC) have a more favorable prognosis than patients with tumors with intact MMR. In order to obtain further insights on the reasons for this different outcome, we investigated the interplay between MMR genes and TLR4/MyD88 signaling. The cancer genome atlas (TCGA) databases were selected to predict the differential expression of TLR4 in colon cancer and its correlation with MMR genes. Moreover, the expression of MMR genes and TLR4 was evaluated by immunohistochemistry in 113 CRC samples and a cohort of 63 patients was used to assess TLR4 mRNA expression and MLH1 epigenetic silencing status. In vitro, the effect of MLH1 knockdown on TLR4 expression was quantified by Real Time PCR. TLR4 expression resulted dependent on MMR status and directly correlated to MLH1 expression. In vitro, MLH1 silencing decreased TLR4 expression. These observations may reflect the better prognosis and the chemoresistance of patients with CRC and MMR defects.

scholarly journals Identification of intestinal flora-related key genes and therapeutic drugs in colorectal cancer

2020 ◽  
Author(s):  
Jiayu Zhang ◽  
Huaiyu Zhang ◽  
Faping Li ◽  
Zheyu Song ◽  
Yezhou Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Flora ◽  
Interaction Network ◽  
Gene Interaction ◽  
The Cancer Genome Atlas ◽  
Interaction Database ◽  
Therapeutic Drugs ◽  
Cancer Genome Atlas ◽  
Key Genes ◽  
Genome Atlas

Abstract Background: Colorectal cancer (CRC) is a multifactorial tumor and a leading cause of cancer-specific deaths worldwide. Recent research has shown that the alteration of intestinal flora contributes to the development of CRC. However, the molecular mechanism by which intestinal flora influences the pathogenesis of CRC remains unclear. This study aims to explore the key genes underlying the effect of intestinal flora on CRC and therapeutic drugs for CRC.Methods: Intestinal flora-related genes were determined using text mining. Based on The Cancer Genome Atlas database, differentially expressed genes (DEGs) between CRC and normal samples were identified with the limma package of the R software. Then, the intersection of the two gene sets was selected for enrichment analyses using the tool Database for Annotation, Visualization and Integrated Discovery. Protein interaction network analysis was performed for identifying the key genes using STRING and Cytoscape. The correlation of the key genes with overall survival of CRC patients was analyzed. Finally, the key genes were queried against the Drug-Gene Interaction database to find drug candidates for treating CRC.Results: 518 genes associated with intestinal flora were determined by text mining. Based on The Cancer Genome Atlas database, we identified 48 DEGs associated with intestinal flora, including 25 up-regulated and 23 down-regulated DEGs in CRC. The enrichment analyses indicated that the selected genes were mainly involved in cell-cell signaling, immune response, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. The protein-protein interaction network was constructed with 13 nodes and 35 edges. Moreover, 8 genes in the significant cluster were considered as the key genes and chemokine (C-X-C motif) ligand 8 (CXCL8) correlated positively with the overall survival of CRC patients. Finally, a total of 24 drugs were predicted as possible drugs for CRC treatment using the Drug-Gene Interaction database.Conclusions: These findings of this study may provide new insights into CRC pathogenesis and treatments. The prediction of drug-gene interaction is of great practical significance for exploring new drugs or novel targets for existing drugs.

scholarly journals CpG-methylation-based risk score predicts progression in colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 605-615 ◽  
Author(s):  
Yao Deng ◽  
Hao Wan ◽  
Jianbo Tian ◽  
Xiang Cheng ◽  
Meilin Rao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Area Under The Curve ◽  
The Cancer Genome Atlas ◽  
Free Interval ◽  
Future Clinical Practice ◽  
Risk Of Progression ◽  
Precision Therapy ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: To identify patients with colorectal cancer (CRC) who are at a truly higher risk of progression, which is key for individualized approaches to precision therapy. Materials & methods: We developed a predictor associated with progression-free interval (PFI) using The Cancer Genome Atlas CRC methylation data. Results: The risk score was associated with PFI in the whole cohort (p < 0.001). A nomogram consisting of the risk score and other significant clinical features was generated to predict the 3- and 5-year PFI in the whole set (area under the curve: 0.79 and 0.71, respectively). Conclusion: The risk score based on 23 DNA-methylation sites may serve as the basis for improved prediction of progression in patients with CRC in future clinical practice.

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