Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study

Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Ohmomo, Hideki [verfasserIn] Komaki, Shohei Sutoh, Yoichi Hachiya, Tsuyoshi Ono, Kanako Arai, Eri Fujimoto, Hiroyuki Yoshida, Teruhiko Kanai, Yae Asahi, Koichi Sasaki, Makoto Shimizu, Atsushi

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Clear cell renal cell carcinoma DNA methylation biomarker Targeted bisulfite sequencing Epigenome-wide association study Whole blood-based

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Epigenetics Communications - BioMed Central, 2021, 2(2022), 1 vom: 02. Mai
Übergeordnetes Werk:	volume:2 ; year:2022 ; number:1 ; day:02 ; month:05

Links:	Volltext

DOI / URN:	10.1186/s43682-022-00009-7

Katalog-ID:	SPR050683519

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520			\|a Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies.
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allfields	10.1186/s43682-022-00009-7 doi (DE-627)SPR050683519 (SPR)s43682-022-00009-7-e DE-627 ger DE-627 rakwb eng Ohmomo, Hideki verfasserin aut Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213 Komaki, Shohei aut Sutoh, Yoichi aut Hachiya, Tsuyoshi aut Ono, Kanako aut Arai, Eri aut Fujimoto, Hiroyuki aut Yoshida, Teruhiko aut Kanai, Yae aut Asahi, Koichi aut Sasaki, Makoto aut Shimizu, Atsushi (orcid)0000-0001-8307-2461 aut Enthalten in Epigenetics Communications BioMed Central, 2021 2(2022), 1 vom: 02. Mai (DE-627)1789629667 2730-7034 nnns volume:2 year:2022 number:1 day:02 month:05 https://dx.doi.org/10.1186/s43682-022-00009-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2022 1 02 05
spelling	10.1186/s43682-022-00009-7 doi (DE-627)SPR050683519 (SPR)s43682-022-00009-7-e DE-627 ger DE-627 rakwb eng Ohmomo, Hideki verfasserin aut Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213 Komaki, Shohei aut Sutoh, Yoichi aut Hachiya, Tsuyoshi aut Ono, Kanako aut Arai, Eri aut Fujimoto, Hiroyuki aut Yoshida, Teruhiko aut Kanai, Yae aut Asahi, Koichi aut Sasaki, Makoto aut Shimizu, Atsushi (orcid)0000-0001-8307-2461 aut Enthalten in Epigenetics Communications BioMed Central, 2021 2(2022), 1 vom: 02. Mai (DE-627)1789629667 2730-7034 nnns volume:2 year:2022 number:1 day:02 month:05 https://dx.doi.org/10.1186/s43682-022-00009-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2022 1 02 05
allfields_unstemmed	10.1186/s43682-022-00009-7 doi (DE-627)SPR050683519 (SPR)s43682-022-00009-7-e DE-627 ger DE-627 rakwb eng Ohmomo, Hideki verfasserin aut Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213 Komaki, Shohei aut Sutoh, Yoichi aut Hachiya, Tsuyoshi aut Ono, Kanako aut Arai, Eri aut Fujimoto, Hiroyuki aut Yoshida, Teruhiko aut Kanai, Yae aut Asahi, Koichi aut Sasaki, Makoto aut Shimizu, Atsushi (orcid)0000-0001-8307-2461 aut Enthalten in Epigenetics Communications BioMed Central, 2021 2(2022), 1 vom: 02. Mai (DE-627)1789629667 2730-7034 nnns volume:2 year:2022 number:1 day:02 month:05 https://dx.doi.org/10.1186/s43682-022-00009-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2022 1 02 05
allfieldsGer	10.1186/s43682-022-00009-7 doi (DE-627)SPR050683519 (SPR)s43682-022-00009-7-e DE-627 ger DE-627 rakwb eng Ohmomo, Hideki verfasserin aut Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213 Komaki, Shohei aut Sutoh, Yoichi aut Hachiya, Tsuyoshi aut Ono, Kanako aut Arai, Eri aut Fujimoto, Hiroyuki aut Yoshida, Teruhiko aut Kanai, Yae aut Asahi, Koichi aut Sasaki, Makoto aut Shimizu, Atsushi (orcid)0000-0001-8307-2461 aut Enthalten in Epigenetics Communications BioMed Central, 2021 2(2022), 1 vom: 02. Mai (DE-627)1789629667 2730-7034 nnns volume:2 year:2022 number:1 day:02 month:05 https://dx.doi.org/10.1186/s43682-022-00009-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2022 1 02 05
allfieldsSound	10.1186/s43682-022-00009-7 doi (DE-627)SPR050683519 (SPR)s43682-022-00009-7-e DE-627 ger DE-627 rakwb eng Ohmomo, Hideki verfasserin aut Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213 Komaki, Shohei aut Sutoh, Yoichi aut Hachiya, Tsuyoshi aut Ono, Kanako aut Arai, Eri aut Fujimoto, Hiroyuki aut Yoshida, Teruhiko aut Kanai, Yae aut Asahi, Koichi aut Sasaki, Makoto aut Shimizu, Atsushi (orcid)0000-0001-8307-2461 aut Enthalten in Epigenetics Communications BioMed Central, 2021 2(2022), 1 vom: 02. Mai (DE-627)1789629667 2730-7034 nnns volume:2 year:2022 number:1 day:02 month:05 https://dx.doi.org/10.1186/s43682-022-00009-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2022 1 02 05
language	English
source	Enthalten in Epigenetics Communications 2(2022), 1 vom: 02. Mai volume:2 year:2022 number:1 day:02 month:05
sourceStr	Enthalten in Epigenetics Communications 2(2022), 1 vom: 02. Mai volume:2 year:2022 number:1 day:02 month:05
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Clear cell renal cell carcinoma DNA methylation biomarker Targeted bisulfite sequencing Epigenome-wide association study Whole blood-based
isfreeaccess_bool	true
container_title	Epigenetics Communications
authorswithroles_txt_mv	Ohmomo, Hideki @@aut@@ Komaki, Shohei @@aut@@ Sutoh, Yoichi @@aut@@ Hachiya, Tsuyoshi @@aut@@ Ono, Kanako @@aut@@ Arai, Eri @@aut@@ Fujimoto, Hiroyuki @@aut@@ Yoshida, Teruhiko @@aut@@ Kanai, Yae @@aut@@ Asahi, Koichi @@aut@@ Sasaki, Makoto @@aut@@ Shimizu, Atsushi @@aut@@
publishDateDaySort_date	2022-05-02T00:00:00Z
hierarchy_top_id	1789629667
id	SPR050683519
language_de	englisch
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More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. 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author	Ohmomo, Hideki
spellingShingle	Ohmomo, Hideki misc Clear cell renal cell carcinoma misc DNA methylation biomarker misc Targeted bisulfite sequencing misc Epigenome-wide association study misc Whole blood-based Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
authorStr	Ohmomo, Hideki
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topic_title	Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study Clear cell renal cell carcinoma (dpeaa)DE-He213 DNA methylation biomarker (dpeaa)DE-He213 Targeted bisulfite sequencing (dpeaa)DE-He213 Epigenome-wide association study (dpeaa)DE-He213 Whole blood-based (dpeaa)DE-He213
topic	misc Clear cell renal cell carcinoma misc DNA methylation biomarker misc Targeted bisulfite sequencing misc Epigenome-wide association study misc Whole blood-based
topic_unstemmed	misc Clear cell renal cell carcinoma misc DNA methylation biomarker misc Targeted bisulfite sequencing misc Epigenome-wide association study misc Whole blood-based
topic_browse	misc Clear cell renal cell carcinoma misc DNA methylation biomarker misc Targeted bisulfite sequencing misc Epigenome-wide association study misc Whole blood-based
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title	Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
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title_full	Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
author_sort	Ohmomo, Hideki
journal	Epigenetics Communications
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author_browse	Ohmomo, Hideki Komaki, Shohei Sutoh, Yoichi Hachiya, Tsuyoshi Ono, Kanako Arai, Eri Fujimoto, Hiroyuki Yoshida, Teruhiko Kanai, Yae Asahi, Koichi Sasaki, Makoto Shimizu, Atsushi
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title_sort	potential dna methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
title_auth	Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
abstract	Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. © The Author(s) 2022
abstractGer	Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. © The Author(s) 2022
abstract_unstemmed	Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p < 1.75 × $ 10^{−8} $); four were reproducible in the replication phase (p < 2.96 × $ 10^{−8} $). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies. © The Author(s) 2022
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title_short	Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study
url	https://dx.doi.org/10.1186/s43682-022-00009-7
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author2	Komaki, Shohei Sutoh, Yoichi Hachiya, Tsuyoshi Ono, Kanako Arai, Eri Fujimoto, Hiroyuki Yoshida, Teruhiko Kanai, Yae Asahi, Koichi Sasaki, Makoto Shimizu, Atsushi
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Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study

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