Discovery and Validation of Hypermethylated Markers for Colorectal Cancer

Wei, Jiaojiao; Li, Guodong; Dang, Shuwei; Zhou, Yong Jin; Zeng, Kai; Liu, Ming

doi:10.1155/2016/2192853

Cited by 19 publications

(29 citation statements)

References 23 publications

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“…We also applied a regularized Cox regression method, which was developed mainly based on LASSO regression, to select 26 important DNA methylation probes with non-zero coefficients from the identified 340 DNA methylation sites (see Materials and Methods; Table S6). Among these 26 significant probes, the change in DNA methylation of some members was reported to be potential indicators of some cancer types, such as PLEKHA6 [18], MARVELD1 [14], MST1R [19], LTBP1 [20], CLIC3 [21], SLC13A5 [22], SFRP5 [23], CPXM1 [24], and AKR1B1 [25]. After that, we introduced a risk score, which was defined as a linear combination of the β -values and the corresponding coefficients of these 26 DNA methylation probes derived from regularized Cox regression (see Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression

Zhou

Guo

2019

Genes

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The progression of bladder cancer is generally a complex and dynamic process, involving a variety of biological factors. Here, we aimed to identify a set of survival-related genes that play an important role in the progression of bladder cancer and uncover their synergistic patterns. Based on the large-scale genomic profiling data and clinical information of 404 bladder cancer patients derived from The Cancer Genome Atlas (TCGA) database, we first discovered 1078 survival-related genes related to their survival states using univariate and multivariate Cox proportional hazardous regression. We then investigated the dynamic changes of the cooperative behaviors of these 1078 genes by analyzing their respective genomic features, including copy number variations, DNA methylations, somatic mutations, and microRNA regulatory networks. Our analyses showed that during the progression of bladder cancer, the biological disorder involving the identified survival-related genes can be reflected by multiple levels of abnormal gene regulation, ranging from genomic alteration to post-transcriptional dysregulation. In particular, the stage-specific co-expression networks of these genes undergo a series of structural variations. Our findings provide useful hints on understanding the underlying complex molecular mechanisms related to the evolution of bladder cancer and offer a new perspective on clinical diagnosis and treatment of bladder cancer.

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Section: Resultsmentioning

confidence: 99%

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression

Zhou

Guo

2019

Genes

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“…As expected, most of the members with shortened 3′UTR in the panel were tumor‐associated genes. ADD2 has conserved 3′UTR isoforms, and the DNA methylation status of ADD2 is a screening marker of colorectal cancer . IL21R is highly expressed in TNBC and enhances the invasion and migration of IL21R+ breast cancer cells in a dose‐dependent manner .…”

Section: Discussionmentioning

confidence: 99%

Integrative 3′ Untranslated Region-Based Model to Identify Patients with Low Risk of Axillary Lymph Node Metastasis in Operable Triple-Negative Breast Cancer

Wang

et al. 2018

The Oncologist

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Currently, sentinel lymph node biopsy is the standard approach for surgical staging in breast cancer patients with negative axillae. Prediction estimation for lymph node metastasis of breast cancer relies on clinicopathological characteristics, which is unreliable, especially in triple-negative breast cancer (TNBC)-a highly heterogeneous disease. The authors developed and validated an effective prediction model for the lymph node status of patients with TNBC, which integrates 3'UTR markers and tumor size. This is the first 3'UTR-based model that will help identify TNBC patients with low risk of nodal involvement who are most likely to benefit from exemption axillary surgery.

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“…Let β = (β 0 , β 1 , β 2 , β 3 ), γ = (σ 2 , τ, υ, Σ) and µ be the vector of the fixed effects, the vector of variance components and the LGF, respectively. Integrating out the random-effects AMP i , CpG j and CpG * j , (2)-(5) can be rewritten in a more compact formulation that encompasses all models considered y ij |β, γ, µ ∼ π(y ij |β, γ, µ), (6)…”

Section: Methylcalmentioning

confidence: 99%

“…This mechanism implies the addition of a methyl group to the 5'-carbon of cytosine in a CpG dinucleotide to form 5-methylcytosine (5-mC) (5). Modifications in DNA methylation could affect gene expression as reported in several types of diseases (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

MethylCal: Bayesian calibration of methylation levels

Ochoa

Zuber

Fernández-Jiménez

et al. 2019

Preprint

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Bisulfite amplicon sequencing has become the primary choice for single-base methylation quantification of multiple targets in parallel. The main limitation of this technology is a preferential amplification of an allele and strand in the PCR due to methylation state. This effect, known as “PCR bias”, causes inaccurate estimation of the methylation levels and calibration methods based on standard controls have been proposed to correct for it. Here, we present a Bayesian calibration tool, MethylCal, which can analyse jointly all CpGs within a DMR or CpG island, avoiding “one-at-a-time” CpG calibration. This enables more precise modeling of the methylation levels observed in the standard controls. It also provides accurate predictions of the methylation levels not considered in the controlled experiment, a feature that is paramount in the derivation of the corrected methylation degree. We tested the proposed method on eight independent assays (two CpG islands and six imprinting DMRs) and demonstrated its benefits, including the ability to detect outliers. We also evaluated MethylCal’s calibration in two practical cases, a clinical diagnostic test on 18 patients potentially affected by Beckwith-Wiedemann syndrome, and 17 individuals with celiac disease. The calibration of the methylation levels obtained by MethylCal allows a clearer identification of patients undergoing loss or gain of methylation in borderline cases and could influence further clinical or treatment decisions. MethylCal is availability as an R package onhttps://github.com/lb664/MethylCal.

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Discovery and Validation of Hypermethylated Markers for Colorectal Cancer

Cited by 19 publications

References 23 publications

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression

Integrative Analysis of Genomic and Clinical Data Reveals Intrinsic Characteristics of Bladder Urothelial Carcinoma Progression

Integrative 3′ Untranslated Region-Based Model to Identify Patients with Low Risk of Axillary Lymph Node Metastasis in Operable Triple-Negative Breast Cancer

MethylCal: Bayesian calibration of methylation levels

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