Epigenetically regulated gene expression profiles reveal four molecular subtypes with prognostic and therapeutic implications in colorectal cancer

2020 ◽  
Author(s):  
Xiaokang Wang ◽  
Jinfeng Liu ◽  
Danwen Wang ◽  
Maohui Feng ◽  
Xiongzhi Wu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Metabolic Activity ◽  
Poor Prognosis ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Epigenetic Mechanisms ◽  
Regulated Gene Expression ◽  
Marked Proliferation

Abstract Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity.

scholarly journals Bioinformatics Analysis of Genes Upregulating Poor Prognosis In Colorectal Cancer And Gastric Cancer

2021 ◽  
Author(s):  
Ruizhi Dong ◽  
Shaodong Li ◽  
Bin Liang ◽  
Zhenhua Kang
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Survival Rate ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Venn Diagram ◽  
Expression Levels ◽  
Significant Difference

Abstract Purpose : To analyze the up-regulated genes of poor prognosis in colorectal cancer and gastric cancer by bioinformatics. Methods: We searched the gene expression profiles GSE156355 and GSE64916 in colorectal cancer and gastric cancer tissues in NCBI-GEO. With P value < 0.05 and log2>1 as the standard, Venn diagram software was used to identify the common DEGs in the two data sets. Kaplan Meier plotter was used to analyze the survival rate data of common differentially expressed genes, draw and select survival curves, and analyze their expression levels. Results: A total of 97 genes were detected to be up-regulated in the two gene expression profiles. There were 19 genes in the prognosis of gastric cancer and 15 genes in the prognosis of colorectal cancer that had significant differences in the survival rate. Among them, KCNQ1, TRIM29, GART, MSX1, SNAI1, SUV39H2, LOXL2 and KCTD14 significantly decreased the survival rate of gastric cancer and colorectal cancer. The expression of MSX1 was the highest in gastric cancer. The expression level of KCTD14 was the highest in colorectal cancer, and there was no significant difference in the expression levels of other genes. Conclusion: There are 19 and 15 genes with significantly different prognostic viability in gastric cancer and colorectal cancer, respectively. The survival rates of KCNQ1, TRIM29, GART, Msx1, SNAI1, SUV39H2, LOXL2 and KCTD14 were significantly decreased in gastric cancer and colorectal cancer. The expression of MSX1 was the highest in gastric cancer. The expression of KCTD14 was the highest in colorectal cancer.

scholarly journals Consensus molecular subtypes of primary colon tumors and their hepatic metastases

2021 ◽  
pp. FSO722
Author(s):  
Yee Chen Lau ◽  
Sebastian Schmeier ◽  
Frank Frizelle ◽  
Rachel Purcell
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Hepatic Metastases ◽  
Gene Expression Profiles ◽  
Colorectal Tumors ◽  
Primary Colorectal Cancer ◽  
Primary Tumors ◽  
Primary Colon

Aim: This pilot study aimed to evaluate the congruency in consensus molecular subtypes (CMS) of primary colorectal cancer and corresponding hepatic metastasis (HM). Materials & methods: RNA was extracted from both primary colorectal cancer and HM from ten patients, sequenced to establish gene-expression profiles and classified into CMS. Clinical data were collected retrospectively. Results: Of the ten patients recruited, nine had primary tumors that were classifiable: seven were CMS2, one was CMS3 and one was CMS4. Five had incongruent classification in the corresponding HM. Three out of the five patients with incongruent classification had received adjuvant chemotherapy prior to hepatic resection. Conclusion: A change in CMS type between matched primary and metastatic colorectal tumors is common and may be attributable to chemotherapy.

Gene Expression Profiles as Predictors of Poor Outcomes in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis

2009 ◽  
Vol 8 (4) ◽  
pp. 207-214 ◽  
Author(s):  
An-Ting T. Lu ◽  
Shelley R. Salpeter ◽  
Anthony E. Reeve ◽  
Steven Eschrich ◽  
Patrick G. Johnston ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Systematic Review ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Profiles ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer ◽  
Poor Outcomes

Analysis of Gene Expression Profiles Reveals Novel Correlations With the Clinical Course of Colorectal Cancer

2007 ◽  
Vol 16 (11) ◽  
pp. 535-548 ◽  
Author(s):  
Duccio Cavalieri ◽  
Piero Dolara ◽  
Enrico Mini ◽  
Cristina Luceri ◽  
Cinzia Castagnini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Clinical Course ◽  
Expression Profiles ◽  
Gene Expression Profiles

Abstract 5711: Gene expression profiles inBRAF V600Emutant colorectal cancer and association withSFRP2methylation status

2017 ◽  
Author(s):  
Kazuya Yasui ◽  
Takeshi Nagasaka ◽  
Toshiaki Toshima ◽  
Takashi Kawai ◽  
Kunitoshi Shigeyasu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Cilium Expression Score Predicts Glioma Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Srinivas Rajagopalan ◽  
Amartya Singh ◽  
Hossein Khiabanian
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Poor Survival ◽  
Aggressive Tumors ◽  
Regulated Gene Expression ◽  
Upregulated Genes ◽  
Expression Score

The accurate classification, prognostication, and treatment of gliomas has been hindered by an existing cellular, genomic, and transcriptomic heterogeneity within individual tumors and their microenvironments. Traditional clustering is limited in its ability to distinguish heterogeneity in gliomas because the clusters are required to be exclusive and exhaustive. In contrast, biclustering can identify groups of co-regulated genes with respect to a subset of samples and vice versa. In this study, we analyzed 1,798 normal and tumor brain samples using an unsupervised biclustering approach. We identified co-regulated gene expression profiles that were linked to proximally located brain regions and detected upregulated genes in subsets of gliomas, associated with their histologic grade and clinical outcome. In particular, we present a cilium-associated signature that when upregulated in tumors is predictive of poor survival. We also introduce a risk score based on expression of 12 cilium-associated genes which is reproducibly informative of survival independent of other prognostic biomarkers. These results highlight the role of cilia in development and progression of gliomas and suggest potential therapeutic vulnerabilities for these highly aggressive tumors.

The relationship between tumor budding, tumor microenvironment, and survival in patients with primary operable colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 581-581
Author(s):  
Hester Catharina Van Wyk ◽  
Antonia K. Roseweir ◽  
Ditte Anderson ◽  
Elizabeth Sutton ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Differential Gene Expression ◽  
Evaluation Method ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Venous Invasion ◽  
Tumour Microenvironment ◽  
Differential Gene ◽  
Tumour Budding

581 Background: Tumour budding is an independent prognostic factor in colorectal cancer and has recently been defined by the International Consensus Conference on Tumour Budding. The aim was to use the ITBCC budding evaluation method to examine relationships between tumour budding, tumour factors, tumour microenvironment, gene expression profiles and survival in patients with primary operable CRC. Methods: Hematoxylin and Eosin (H&E) stained slides of 953 CRC patients, diagnosed between 1997 and 2007 were evaluated for tumour budding according to the ITBCC-criteria. The tumour microenvironment was evaluated using tumour stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumour inflammatory cell infiltrate. Differential gene expression was assessed using TempO-Seq gene expression profiling (BioSpyder Technologies Inc., CA, USA) using the Surrogate+Tox targeted panel (2,733 genes selected for biological diversity, maximal information content, and widespread pathway coverage). Results: High budding (n = 269/ 28%) was significantly associated with TNM stage (P < 0.001), venous invasion (P < 0.001), weak KM grade (P < 0.001), high TSP (P < 0.001) and reduced cancer specific survival (CSS) (HR = 5.04; 95% confidence interval [CI], 3.50-9.51; P < 0.001) and was independent of venous invasion, KM grade, and Ki67 proliferation index. RNA expression analysis was employed using TempO-Seq to determine differential gene expression between tumours with (n = 8) and without budding (n = 18). Three genes were identified as significantly differentially expressed: S100A2 (S100 calcium binding protein A2) was upregulated by 2.9 fold (padj < 0.00001); REG1A (regenerating family member 1 alpha) was downregulated by 4.7 fold (padj < 0.01) and LCN2 (lipocalin 2) was downregulated by 2.2 fold (padj < 0.01). Conclusions: Tumour budding stratifies patients’ survival in primary operable colorectal cancer and associates with differing gene expression profiles and factors of the tumour. Therefore, the ITBCC budding evaluation method should be used to assess tumour budding as supplement the TNM staging system and can help to further subdivide colorectal cancer into new prognostic groups.

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