scholarly journals Genome-wide analysis of DNA methylation identifies two CpG sites for the early screening of colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 37-52 ◽  
Author(s):  
Xiaokang Wang ◽  
Danwen Wang ◽  
Haoran Zhang ◽  
Maohui Feng ◽  
Xiongzhi Wu

Aim: To identify a panel of DNA methylation markers for the early diagnosis of colorectal cancer (CRC). Materials & methods: Using public omics data and our pyrosequencing data, we developed and validated a global methylation model and a CpG-methylation-based model for CRC screening. Results: Both of the models yielded high sensitivity and specificity for distinguishing CRC and its precursors (colorectal adenoma and colorectal laterally spreading tumor) from normal controls in eight independent datasets and our newly collected samples. More importantly, the two-CpG-based model showed high specificity in excluding inflammatory bowel diseases and other 13 cancer types. Conclusion: A diagnostic model based on two CpGs (cg09239744 and cg12587766) may be a powerful tool for CRC screening.

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1539
Author(s):  
Yi-Chiao Cheng ◽  
Po-Hsien Wu ◽  
Yen-Ju Chen ◽  
Cing-Han Yang ◽  
Jhen-Li Huang ◽  
...  

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.


Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 569
Author(s):  
Benjamin E. Ansa ◽  
Nicollette Lewis ◽  
Zachary Hoffman ◽  
Biplab Datta ◽  
J. Aaron Johnson

Colorectal cancer (CRC) is the third most prevalent cancer and the second most common cause of cancer-related deaths in the United States (USA). Early screening has been demonstrated to improve clinical outcomes for CRC. Assessing patterns in CRC screening utilization is important for guiding policy and implementing programs for CRC prevention and control. This study examines the trends and sociodemographic factors associated with blood stool test utilization (BSTU) for CRC screening in Georgia, USA. The Behavioral Risk Factor Surveillance System (BRFSS) data were analyzed for Average Annual Percent Change (AAPC) in BSTU between 1997 and 2014 among adults aged 50+ who have had a blood stool test within the past two years, and logistic regression analysis of the 2016 data was performed to identify the associated sociodemographic factors. In Georgia, an overall decrease was observed in BSTU, from 27.8% in 1997 to 16.1% in 2014 (AAPC = −2.6, p = 0.023). The decrease in BSTU was less pronounced in Georgia than nationally (from 26.1% in 1997 to 12.8% in 2014 (AAPC = −4.5, p < 0.001)). BSTU was significantly associated with black race/ethnicity (Black vs. White (aOR = 1.43, p = 0.015)), older age (≥70 vs. 50–59 (aOR = 1.62, p = 0.006)), having insurance coverage (no vs. yes (aOR = 0.37 p = 0.005)), and lower income (≥USD 50,000 vs. <USD 25,000 (aOR = 0.70 p = 0.050)). These findings reveal a decrease over time in BSTU in Georgia, with existing differences between sociodemographic groups. Understanding these patterns helps in directing tailored programs for promoting CRC screening, especially among disadvantaged populations.


Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Nam-Yun Cho ◽  
Ji-Won Park ◽  
Xianyu Wen ◽  
Yun-Joo Shin ◽  
Jun-Kyu Kang ◽  
...  

Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.


2014 ◽  
Vol 22 (S3) ◽  
pp. 1419-1427 ◽  
Author(s):  
Pei-Ching Lin ◽  
Jen-Kou Lin ◽  
Chien-Hsing Lin ◽  
Hung-Hsin Lin ◽  
Shung-Haur Yang ◽  
...  

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei-Ying Zeng ◽  
Yu-Rong Tan ◽  
Sheng-Feng Long ◽  
Zu-Dong Sun ◽  
Zhen-Guang Lai ◽  
...  

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.


2016 ◽  
Vol 150 (4) ◽  
pp. S456
Author(s):  
David Gibson ◽  
Blathnaid Nolan ◽  
Joanna Rea ◽  
Maire Buckley ◽  
Gareth Horgan ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Asma Althobaiti ◽  
Hoda Jradi

Abstract Background Colorectal cancer (CRC) is a major health problem. It is the third most diagnosed common tumour and the fourth leading cause of cancer-related deaths worldwide. Early screening has been shown to decrease the incidence of CRC cancer and decrease mortality. In Saudi Arabia (SA), there is no national policy for CRC screening despite the growing incidence of the disease. This study investigated the knowledge of risk factors for CRC, recommendations for screening, and attitudes and barriers towards screening among medical students. Methods Data was collected using a self-administered valid and reliable questionnaire consisting of demographic characteristics, knowledge, attitude, and barriers measurements completed by 581 medical students from two Saudi schools. Frequencies and mean scores of knowledge and attitude were determined. The likelihood of students having adequate knowledge of CRC risk factors and screening modalities was estimated using multivariate logistic regression analysis. Results Knowledge of the risk factors for CRC and screening modalities, and attitude towards screening were poor in 52.47 and 57.83% of the surveyed medical students; respectively. Higher level of medical education (OR = 3.23; 95% CI: 2.01–5.18) and a positive attitude towards CRC screening (OR = 2.74; 95% CI: 1.86–4.03) were independent predictors of higher knowledge levels. Lack of awareness about CRC and screening modalities among patients, and shortage of specialized healthcare providers were barriers independently associated with low knowledge levels. Conclusions Saudi medical students have limited knowledge of CRC risk factors of and a poor attitude towards CRC screening. These results contribute to our understanding of missed teaching opportunities in Saudi medical schools and suggest intervening at the medical school, clinical practice, and population levels to increase CRC screening practices.


2019 ◽  
Vol 10 (21) ◽  
pp. 5264-5271 ◽  
Author(s):  
Jie Chen ◽  
Haipeng Sun ◽  
Weisen Tang ◽  
Lin Zhou ◽  
Xi Xie ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3614-3614
Author(s):  
Ana Acuna Villaorduna ◽  
Nishi Shah ◽  
Sanjay Goel

3614 Background: Colorectal cancer (CRC) incidence is increasing in patients younger than 50 years old. Currently, there are discordant recommendations regarding CRC screening: while the American Cancer Society favors to start at age 45, the National Comprehensive Cancer Network and the US Preventive Task Force suggest starting at age 50. This study is aimed to compare the incidence, clinical characteristics and survival of patients diagnosed with standard-onset CRC (SO) versus early-onset colorectal cancer by age-groups. Methods: Patients diagnosed with CRC at ages older than 35 were identified using the SEER registry and categorized into four groups based on age at diagnosis. EO1 (35-39), EO2 (40-44), EO3 (45-49) and SO (>50) years, respectively. Incidence, clinical features and survival were compared among groups. Results: 178 678 patients were identified. 9.2% were diagnosed before 50 years. Of these, 1.4%, 2.8% and 5.1% were EO1, EO2 and EO3; respectively. Patients with early-onset CRC (EO) had higher frequency of Hispanics (13.9% vs. 8.4%, p<0.01), stage IV (24.8% vs. 17.3%, p<0.01), left-sided tumors (74.1% vs. 56.9%, p<0.01) and better survival compared to SO. Among EO groups, the frequency of poor/anaplastic grade was inversely proportional to age; stage IV was similar between EO2 and EO3 and lower in EO1. Black race, grade and stage were predictors of mortality for all EO groups; laterality was a mortality predictor in EO2 and EO3. Conclusions: EO-CRC and SO-CRC have different pathological features that should be considered for CRC screening. Higher rates of stage IV disease are encountered in patients between 40-49 years old; hence early screening should be considered. Given higher rates of left-sided tumors, sigmoidoscopy might be an adequate tool for most patients with EO-CRC. [Table: see text]


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