DNA Methylation in INA , NHLH2 , and THBS4 Is Associated with Metastatic Disease in Renal Cell Carcinoma

The detection of DNA methylation in primary tumor tissues could be relevant for early stratification of aggressive renal cell carcinomas (RCCs) as a basis for future personalized adjuvant therapy. Methylated TCGA KIRC based candidate CpG loci in , and that are possibly associated with RCC metastasis...

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Bibliographic Details
Published in:Cancers 2021-12, Vol.14 (1), p.39
Main Authors: Katzendorn, Olga, Peters, Inga, Dubrowinskaja, Natalia, Moog, Joana M, Reese, Christel, Tezval, Hossein, Faraj Tabrizi, Pouriya, Hennenlotter, Jörg, Lafos, Marcel, Kuczyk, Markus A, Serth, Jürgen
Format: Article
Language:English
Subjects:
Binding sites
Biomarkers
Cancer therapies
Colorectal cancer
CpG islands
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Gene expression
Genomes
Kidney cancer
Mathematical models
Medical prognosis
Metastases
Metastasis
Mutation
Patients
Proteins
Regression analysis
Renal cell carcinoma
Software
Statistical analysis
Tumors
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Summary:The detection of DNA methylation in primary tumor tissues could be relevant for early stratification of aggressive renal cell carcinomas (RCCs) as a basis for future personalized adjuvant therapy. Methylated TCGA KIRC based candidate CpG loci in , and that are possibly associated with RCC metastasis were evaluated by pyrosequencing in 154 paired normal adjacent and primary tumor tissues, as well as in 202 metastatic tissues. Statistical analysis was carried out by bivariate logistic regression for group comparisons, log rank survival analysis, and unsupervised and supervised analysis for the classification of tumors. Increased methylation of , and loci were significantly associated with distant metastasis in primary tumors ( < 0.05), tissue-specific hypermethylation in metastatic ( = 7.88 × 10 , 5.57 × 10 , 2.06 × 10 ) and tumor tissues ( = 3.72 × 10 , 3.17 × 10 , 1.58 × 10 ), and shortened progression free survival in patients ( = 0.03). Combined use of CpG site-specific methylation permits the discrimination of tissues with metastatic disease and reveals a significant contribution of CpG sites in all genes to the statistical classification model. Thus, metastasis in RCC is significantly associated with methylation alterations in , and loci, providing independent information for the potential early detection of aggressive renal cancers as a rationale for stratifying patients to adjuvant therapies.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14010039