Long Intergenic Noncoding RNA 299 Methylation in Peripheral Blood is a Biomarker for Triple-Negative Breast Cancer

Bermejo, Justo Lorenzo; Huang, Guanmengqian; Manoochehri, Mehdi; Mesa, Karen; Schick, Matthias; Silos, Rosa González; Ko, Yon; Brüning, Thomas; Brauch, Hiltrud; Lo, Wing Yee; Hoheisel, Jöerg; Hamann, Ute

doi:10.2217/epi-2018-0121

Cited by 30 publications

(31 citation statements)

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“…Proportion of patients presenting invasive breast cancers varied from 88 to 100% ( n = 7 studies), with five studies including exclusively invasive breast cancers [ 18 , 19 , 21 , 30 , 31 ]. Proportion of ER-positive breast cancers varied from 0 to 83% ( n = 7 studies), with only two studies including at least 80% of ER-positive breast cancers [ 30 , 32 ], and one study including exclusively ER-negative breast cancers [ 22 ] (Table 1 and Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…The other 10 probe-wise differential methylation analyses identified between one and 806 DMP (median = 24 DMP) with no overlapping DMP between different studies. Five genes overlapped between two different studies but differed in the identified DMP, namely: GRB10 [ 18 , 25 ], RPH3AL [ 18 , 25 ], SEMA5A [ 25 , 33 ], C7orf50 [ 25 , 27 ] and XYLT1 [ 22 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

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Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

et al. 2020

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Background DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses. Methods We searched major databases (MEDLINE, EMBASE, Web of Science, CENTRAL) from inception up to 30th June 2019, for observational or intervention studies investigating the association between epigenome-wide DNA methylation (using the HM450k or EPIC BeadChip), measured in any type of human sample, and breast cancer risk. A pre-established protocol was drawn up following the Cochrane Reviews rigorous methodology. Study selection, data abstraction, and risk of bias assessment were performed by at least two investigators. A qualitative synthesis and systematic comparison of the strengths and weaknesses of studies was performed. Results Overall, 20 studies using the HM450k BeadChip were included, 17 of which had measured blood-derived DNA methylation. There was a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer. The strength of associations was modest for global hypomethylation and relatively weak for most of epigenetic age algorithms. Differences in length of follow-up periods may have influenced the ability to detect associations, as studies reporting follow-up periods shorter than 10 years were more likely to observe an association with global DNA methylation. Probe-wise differential methylation analyses identified between one and 806 differentially methylated CpGs positions in 10 studies. None of the identified differentially methylated sites overlapped between studies. Three studies used breast tissue DNA and suffered major methodological issues that precludes any conclusion. Overall risk of bias was critical mainly because of incomplete control of confounding. Important issues relative to data preprocessing could have limited the consistency of results. Conclusions Global DNA methylation may be a short-term predictor of breast cancer risk. Further studies with rigorous methodology are needed to determine spatial distribution of DNA hypomethylation and identify differentially methylated sites associated with risk of breast cancer. Prospero registration number CRD42020147244

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

et al. 2020

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“…In addition, a 3‐lncRNA signature obtained using the logistic model exhibited excellent diagnostic values with an AUC of 0.934 112 . In addition, an epigenome‐wide association study (EWAS) conducted by Bermejo et al 113 revealed that hypermethylation of LINC00299 in the peripheral blood of TNBC patients could function as a useful circulating biomarker for TNBC and exhibited excellent diagnostic value. Jiang et al 114 proposed an integrated mRNA‐lncRNA signature based on a combination of mRNA and lncRNA species and found that lncRNA HIF1A‐AS2 and AK124454 could be involved in mediating TNBC cell proliferation, invasion and paclitaxel resistance and also exhibited good prognostic value.…”

Section: Long Non‐coding Rnasmentioning

confidence: 98%

“…Besides, the dysregulated lncRNA ANRIL, HIF1A‐AS2 and UCA1 can be detected in plasma of TNBC patients and the 3‐lncRNAs combined signature exhibited excellent diagnostic value 112 . Moreover, even hypermethylation of LINC00299 in peripheral blood of TNBC patients also served as a useful circulating biomarker for TNBC 113 . However, the circulating circRNAs have not been found to be biomarkers in TNBC.…”

Section: Perspectives In Clinical Practicementioning

confidence: 99%

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

et al. 2020

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Triple‐negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with negativity for oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2). Non‐coding RNAs (ncRNAs) make up most of the transcriptome and are widely present in eukaryotic cells. In recent years, emerging evidence suggests that ncRNAs, mainly microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), play prominent roles in the tumorigenesis and development of TNBC, but the functions of most ncRNAs have not been fully described. In this review, we systematically elucidate the general characteristics and biogenesis of miRNAs, lncRNAs and circRNAs, discuss the emerging functions of these ncRNAs in TNBC and present future perspectives in clinical practice.

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“…Using a retrospective study design, we recently identified and validated a region within the long noncoding RNA 299 ( LINC00299 ) gene that showed a higher methylation (3% in the discovery set and 2% in the validation set) in PBL DNA from TNBC patients compared with healthy controls 17 , suggesting that this may be a biomarker for TNBC. The hypermethylated region is located in a putative regulatory region of the LINC00299 gene, the function of which is unknown.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study

Manoochehri

Jones

Tomczyk

et al. 2020

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Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with a high rate of recurrence and poor prognosis. Recently we identified a hypermethylation in the long noncoding RNA 299 ( LINC00299 ) gene in blood-derived DNA from TNBC patients compared with healthy controls implying that LINC00299 hypermethylation may serve as a circulating biomarker for TNBC. In the present study, we investigated whether LINC00299 methylation is associated with TNBC in a prospective nested breast cancer case–control study within the Generations Study. Methylation at cg06588802 in LINC00299 was measured in 154 TNBC cases and 159 breast cancer-free matched controls using MethyLight droplet digital PCR. To assess the association between methylation level and TNBC risk, logistic regression was used to calculate odd ratios and 95% confidence intervals, adjusted for smoking status. We found no evidence for association between methylation levels and TNBC overall ( P = 0.062). Subgroup analysis according to age at diagnosis and age at blood draw revealed increased methylation levels in TNBC cases compared with controls in the young age groups [age 26–52 ( P = 0.0025) and age 22–46 ( P = 0.001), respectively]. Our results suggest a potential association of LINC00299 hypermethylation with TNBC in young women.

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Long Intergenic Noncoding RNA 299 Methylation in Peripheral Blood is a Biomarker for Triple-Negative Breast Cancer

Abstract: Hypermethylation of LINC00299 in peripheral blood may constitute a useful circulating biomarker for TNBC.

Cited by 30 publications

References 50 publications

Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study

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