Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS)
Abstract
:1. Introduction
2. Results
2.1. In Silico Identification of the Association of NKX6-2 Loci Methylation and State of Distant Metastasis
2.2. Evaluation of NKX6-2 Candidate Loci in Primary RCC, RCC-Associated Metastatic Tissues, and Cell Models
2.3. Similar CpG-Specific Methylation in Metastatic Primary Tumor Tissues and Metastatic Tissues
2.4. Development and Evaluation of a RMAMS
3. Discussion
4. Material and Methods
4.1. Study Design
4.2. Study Cohort
4.3. Nucleic Acid Extraction, DNA Bisulfite Conversion, and DNA Methylation Analysis
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Pyroassay | Gene | Chromosom | TCGA/KIRC Candidate | Genomic Position | AssayCG |
---|---|---|---|---|---|
NKX6-2 | 10 | cg06082548 | 134,598,909 | ||
R3 | NKX6-2 | 10 | 134,598,942 | CG4 | |
134,598,945 | CG3 | ||||
134,598,948 | CG2 | ||||
134,598,952 | CG1 | ||||
R2 | NKX6-2 | 10 | 134,599,807 | CG5 | |
cg01384488 | 134,599,809 | CG4 | |||
134,599,823 | CG3 | ||||
134,599,836 | CG2 | ||||
134,599,841 | CG1 | ||||
R1 | NKX6-2 | 10 | cg19701540 | 134,600,915 | CG1 |
134,600,919 | CG2 | ||||
134,600,922 | CG3 | ||||
134,600,932 | CG4 | ||||
134,600,934 | CG5 | ||||
134,600,938 | CG6 | ||||
134,600,949 | CG7 |
Assay | Tumor Specific Hypermethylation | Metastatic Primary Cancer Hypermethylation | Metastatic Tissue Specific Hypermethylation | ||||||
---|---|---|---|---|---|---|---|---|---|
p-Value 1 | Mean Meth. (%) | OR (95% CI) | p-Value 2 | Mean Meth. (%) | OR (95% CI) | p-Value 2 | |||
M0 | M+ | M0 | Mtx | ||||||
R3 | 6.60 × 10−17 | 14.70 | 23.08 | 1.06 (1.03–1.10) | 3.37 × 10−4 | 14.14 | 23.05 | 1.08 (1.05–1.11) | 1.14 × 10−7 |
R2 | 1.25 × 10−14 | 11.19 | 17.23 | 1.04 (1.01–1.07) | 0.008 | 10.46 | 19.81 | 1.09 (1.06–1.12) | 7.20 × 10−8 |
R1 | 1.16 × 10−14 | 16.31 | 23.35 | 1.04 (1.01–1.07) | 0.006 | 15.82 | 24.81 | 1.05 (1.03–1.07) | 1.04 × 10−5 |
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Serth, J.; Peters, I.; Katzendorn, O.; Dang, T.N.; Moog, J.; Balli, Z.; Reese, C.; Hennenlotter, J.; Grote, A.; Lafos, M.; et al. Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS). Int. J. Mol. Sci. 2022, 23, 11190. https://doi.org/10.3390/ijms231911190
Serth J, Peters I, Katzendorn O, Dang TN, Moog J, Balli Z, Reese C, Hennenlotter J, Grote A, Lafos M, et al. Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS). International Journal of Molecular Sciences. 2022; 23(19):11190. https://doi.org/10.3390/ijms231911190
Chicago/Turabian StyleSerth, Jürgen, Inga Peters, Olga Katzendorn, Tu N. Dang, Joana Moog, Zarife Balli, Christel Reese, Jörg Hennenlotter, Alexander Grote, Marcel Lafos, and et al. 2022. "Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS)" International Journal of Molecular Sciences 23, no. 19: 11190. https://doi.org/10.3390/ijms231911190