scholarly journals The Methylation of SDC2 and TFPI2 Defined Three Methylator Phenotypes of Colorectal Cancer

2021 ◽  
Author(s):  
Ruixue Lei ◽  
Yanteng Zhao ◽  
Kai Huang ◽  
Qian Wang ◽  
Kangkang Wan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Methylation Status ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Tumor Location ◽  
Functional Enrichment ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype ◽  
Almost All

Abstract BackgroudMethylated SDC2 and TFPI2 are applied frequently for the early detection of colorectal cancer (CRC). However, they often miss some positive samples, which directly affects their sensitivities, and the underlining mechanism is not well known.Methods:CRC samples from TCGA and GEO datasets were divided into three groups, Highmethylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Lowmethylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location, and microsatellite instable were then assessed between the three groups and verified in our custom cohort.ResultsSamples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration.Conclusions:The three methylation phenotypes identified based on SDC2 and TFPI2 methylation status showed extensive variations in tumor location, patient age, MSI and ECM biology processes, suggesting that these respective sides should be considered when developing new methylation-based biomarkers for CRC detection.

scholarly journals The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer

2021 ◽  
Author(s):  
Lei Ruixue ◽  
Zhao Yanteng ◽  
Huang Kai ◽  
Wan Kangkang ◽  
Li Tingting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cpg Island ◽  
Methylation Status ◽  
Tumor Location ◽  
Functional Enrichment ◽  
Superior Performance ◽  
Regulation Of Transcription ◽  
Patient Age ◽  
Patient Âgé

Methylation-based noninvasive molecular diagnostics are easy and feasible tools for the early detection of colorectal cancer (CRC). However, many of them have the limitation of low sensitivity with some CRCs detection failed in clinical practice. In this study, the clinical and pathological characteristics, as well as molecular features of three methylator-groups, defined by the promoter methylation status of SDC2 and TFPI2, were investigated in order to improve the performance of CRC detection. The Illumina Infinium 450k Human DNA methylation data and clinical information of CRCs were collected from The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO) database. CRC samples were divided into three groups, HH (dual-positive), HL (single positive) and LL (dual-negative) according to the methylation status of SDC2 and TFPI2 promoters. Differences in age, tumor location, microsatellite instable status and differentially expressed genes (DEGs) were evaluated among the three groups and these findings were then confirmed in our inner CRC dataset. The combination of methylated SDC2 and TFPI2 showed a superior performance of distinguishing CRCs from normal controls than each alone. Samples of HL group were more often originated from left-side CRCs whereas very few of them were from right-side (P < 0.05). HH grouped CRCs showed a higher level of microsatellite instability and mutation load than other two groups (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). All mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were found in HH group (HH/HL/LL: 51/0/0, P = 0.018). Also there was a significantly older patient age at the diagnosis in HH group. Gene expression analysis identified 37, 84 and 22 group-specific DEGs for HH, HL and LL, respectively. Functional enrichment analysis suggested that HH specific DEGs were mainly related to the regulation of transcription and other processes, while LL specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. The three defined mathylator groups showed great difference in tumor location, patient age, MSI and ECM biological process, which could facilitate the development of more effective biomarkers for CRC detection.

scholarly journals Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Julia D Labadie ◽  
Tabitha A Harrison ◽  
Barbara Banbury ◽  
Efrat L Amtay ◽  
Sonja Bernd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Distal Colon ◽  
Tumor Location ◽  
Proximal Colon ◽  
Postmenopausal Hormone Therapy ◽  
Cpg Island Methylator Phenotype ◽  
Tumor Subtypes ◽  
Methylator Phenotype

Abstract Background Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

scholarly journals The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cancer Prognosis ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

scholarly journals CpG Island Methylator Phenotype-Low (CIMP-Low) in Colorectal Cancer: Possible Associations with Male Sex and KRAS Mutations

2006 ◽  
Vol 8 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Shuji Ogino ◽  
Takako Kawasaki ◽  
Gregory J. Kirkner ◽  
Massimo Loda ◽  
Charles S. Fuchs
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Male Sex ◽  
Methylator Phenotype

scholarly journals IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype

2009 ◽  
Vol 31 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Hiromu Suzuki ◽  
Shinichi Igarashi ◽  
Masanori Nojima ◽  
Reo Maruyama ◽  
Eiichiro Yamamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Responsive Gene ◽  
Methylator Phenotype

Determination & expression of chimeric protein in colorectal cancer: A bioinformatics Approach

2021 ◽  
Vol 2 (3) ◽  
pp. 35-67
Author(s):  
Gargi Bhattacharyya ◽  
Amit Chattopadhay
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Therapeutic Process ◽  
Chimeric Protein ◽  
Ageing Population ◽  
Cpg Island Methylator Phenotype ◽  
High Risk Factors ◽  
Bowel Movements ◽  
Methylator Phenotype ◽  
New Treatments

Colorectal cancer (CRC) accounts for about 10% of cancer-related mortality in western countries. Increasing ageing population, undesirable modern dietary and high-risk factors like smoking, obesity and low exercise. Chromosomal instability (CIN), CpG island methylator phenotype (CIMP), and microsatellite instability are the three different mechanism that give rise to CRC. It often grow slowly, and customarily doesn’t produce symptoms until reaching a substantial size of several centimeters, which can block the passage of feces and cause cramping, pain, or bleeding which can present as visible bleeding with bowel movements or, rarely, dark “tarry” stools. Most colon tumors develop via a several different processes involving a series of histological, morphological, and genetical changes that accumulate over time to time. New treatments for primary and metastatic colorectal cancer have emerged, like in variety of therapeutic process by preparing chimeric proteins that triggers the cells and stop it from getting severe.

Lower LINE-1 methylation is associated with promoter hypermethylation and distinct molecular features in gastric cancer

Epigenomics ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1651-1659
Author(s):  
Sayumi Tahara ◽  
Tomomitsu Tahara ◽  
Noriyuki Horiguchi ◽  
Masaaki Okubo ◽  
Tsuyoshi Terada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Cpg Island ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Cpg Island Methylator Phenotype ◽  
Line1 Methylation ◽  
Methylator Phenotype ◽  
H Pylori ◽  
Mlh1 Methylation

Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods: LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori-related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori-related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.

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