Identification of gene-specific DNA methylation signature for Colorectal Cancer

Li, Kaixue; Zeng, Li; Wei, Hong; Hu, Jingjing; Jiao, Lu; Zhang, Juan; Xiong, Ying

doi:10.1016/j.cancergen.2018.05.003

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…These methods are essential tools for researchers and practitioners to characterize the noninvasive tumors, plan for individualized treatments and track tumor treatment efficacy and prognosis in CRC. Of such technics, gene-specific DNA methylation patterning is perhaps the most attractive [6]. DNA methylation mainly occurs in CpG islands and as DNA methylation is more stable in comparison to mutations, it has been considered as a favorable area for biomarker exploration and identification [1,5,6].…”

Section: Introductionmentioning

confidence: 99%

The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours

et al. 2019

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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.

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Section: Introductionmentioning

confidence: 99%

The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours

et al. 2019

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“…Therefore, the therapeutic targets and prognostic biomarkers for gastrointestinal adenocarcinoma at the epigenetic level (e.g., DNA methylation level) remain to be investigated. Several studies have identified gene-specific DNA methylation signatures for OS in gastrointestinal cancers [14][15][16][17] , but no study has classified cancer subtypes or constructed prognostic signatures for gastrointestinal adenocarcinoma based on promoter DNA methylation sites. Here, we assessed the DNA methylation profile and corresponding clinical information of patients with gastrointestinal adenocarcinoma from publicly available databases and identified promoter methylation-based cancer subtypes, as well as hypo-and hyper-methylated site-based signatures for predicting OS of GAC and CAC patients.…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, DNA methylation in gastrointestinal cancers has been extensively studied, especially CpG island methylation, which occurs in 56% of the protein-coding genes in the human genome 10,11 , and the diagnostic potential of certain CpG methylation sites for gastrointestinal cancer has been effectively assessed 12,13 . Moreover, several markers for overall survival (OS) of patients with gastrointestinal cancer have been developed according to transcription and methylation profiles, but these studies were based mostly on analysis of candidate genes and focused mainly on CpG island methylation and its relationship with gene expression [14][15][16][17][18] . However, the DNA methylation-based cancer subtypes and prognostic signatures for gastrointestinal adenocarcinoma have not been fully investigated.…”

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confidence: 99%

Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures

Xiang

2020

Sci Rep

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Gastric adenocarcinoma (GAC) and colon adenocarcinoma (CAC) are the most common gastrointestinal cancer subtypes, with a high incidence and mortality. Numerous studies have shown that its occurrence and progression are significantly related to abnormal DNA methylation, especially CpG island methylation. However, little is known about the application of DNA methylation in GAC and CAC. The methylation profiles were accessed from the Cancer Genome Atlas database to identify promoter methylation-based cancer subtypes and signatures for GAC and CAC. Six hypo-methylated clusters for GAC and six hyper-methylated clusters for CAC were separately generated with different OS profiles, tumor progression became worse as the methylation level decreased in GAC or increased in CAC, and hypomethylation in GAC and hypermethylation in CAC were negatively correlated with microsatellite instability. Additionally, the hypo- and hyper-methylated site-based signatures with high accuracy, high efficiency and strong independence can separately predict the OS of GAC and CAC patients. By integrating the methylation-based signatures with prognosis-related clinicopathologic characteristics, two clinicopathologic-epigenetic nomograms were cautiously established with strong predictive performance and high accuracy. Our research indicates that methylation mechanisms differ between GAC and CAC, and provides novel clinical biomarkers for the diagnosis and treatment of GAC and CAC.

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“…Zong Z et al demonstrated a prognostic alternative splicing signature by differential splicing patterns of 13 genes in CRC [39]. Li K et al revealed a six gene-speci c DNA methylation signature for CRC [40]. Zhou Z et al developed and validated of an autophagy signature based on 5 autophagy genes which could evaluate the survival of CRC patients after surgery [41].…”

Section: Based On the Strati Cation Of Clinical Variables The Correlmentioning

confidence: 99%

A Novel Ferroptosis-related Lncrna Prognostic Signature for Colorectal Cancer by Bioinformatics Analysis

Yang

Zhang

Wang

et al. 2021

Preprint

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Background: Recently, extensive studies have shown that ferroptosis in cancer treatment has been increasingly confirmed. The current study aims to construct a robust ferroptosis-related lncRNAs signature prediction model of colorectal cancer (CRC) patients by bioinformatics analysisMethods: The transcriptome data were abstracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened by comparing 568 CRC tissues with 44 adjacent non-CRC tissues. Univariate Cox regression, lasso regression, multivariate Cox regression were conducted to design a ferroptosis-related lncRNA signature. This signature’s prognosis was verified by the log-rank test of Kaplan-Meier curve and the area under curve (AUC) of receiver operating characteristic (ROC) in train set, test set, and entire set. Furthermore, univariate and multivariate Cox regression were used to analyze its independent prognostic ability. The relationship of the ferroptosis-linked lncRNAs' expression and clinical variables was demonstrated by Wilcoxon rank-sum test and Kruskal-Wallis test. Gene set enrichment analysis (GSEA) was performed to signaling pathways it may involve.Results: 2541 differentially expressed lncRNAs were screened, of which 439 are ferroptosis-related lncRNAs. A seven ferroptosis-related lncRNAs (AC005550.2, LINC02381, AL137782.1, C2orf27A, AC156455.1, AL354993.2, AC008760.1) prognostic signature was constructed, validated and evaluated. This model's prognosis in the high-risk group is obviously worse than that of the low-risk group in train set, test set, and entire set. The AUC of ROC predicting the three years survival in the train set, test set, and entire set was 0.796, 0.715, and 0.758, respectively. Moreover, the designed molecular signature was found to be an independent prognostic variable. Compared to clinical variables, this signature's ROC curves demonstrated the second largest AUC value (0.737). The expression of these lncRNAs and the lncRNA signature are related to distant metastasis, Lymph-node status, clinical stage, T stage, KRAS mutation, BRAF mutation, MMR status, and perineural invasion. Finally, GSEA analysis results show that the signature is involved in six metabolism-related pathways.Conclusion: The current study constructed, validated, and evaluated a seven ferroptosis-related lncRNA signature which can independently be used to predict the prognosis of CRC patients, and it may become a new therapeutic target.

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Identification of gene-specific DNA methylation signature for Colorectal Cancer

Cited by 8 publications

References 23 publications

The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours

The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours

Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures

A Novel Ferroptosis-related Lncrna Prognostic Signature for Colorectal Cancer by Bioinformatics Analysis

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