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

Abstract

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.

Bioinformatics analysis of necroptosis‑related lncRNAs and immune infiltration, and prediction of the prognosis of patients with esophageal carcinoma

“…Chang et al studied the role of the LINC00299/miR-135a-5p/XBP1 axis in the regulation of atherosclerosis progression, ox-LDL-induced oxidative damage, and human aortic vascular smooth muscle cell migration and invasion ( 49 ). Moreover, Manoochehri et al found that the occurrence of TNBC was often accompanied by hypermethylation of LINC00299 in young women, indicating a potential association between them ( 50 ). Talkowski et al found a functional role for these specific noncoding RNAs in brain development in subjects with LINC00299 mutations and raised the possibility that lncRNAs, as a class of abnormalities, might play an important role in human developmental disorders ( 51 ).…”

Secreted Non-Coding RNAs: Functional Impact on the Tumor Microenvironment and Clinical Relevance in Triple-Negative Breast Cancer

“…An epigenome-wide association study (EWAS) conducted on a large cohort of TNBC patients to identify circulating biomarkers showed that LINC00299/ID2 (RNA 299) had a higher methylation in TNBC patients compared with controls [ 93 ]. The fact that hypermethylation of LINC00299 in peripheral blood could represent a useful circulating biomarker for TNBC was also supported by Manoochehri and colleagues who analyzed an additional prospective cohort of patients [ 94 ]. Interestingly, they found a significant association between methylated LINC00299 levels and TNBC subgroup in young age patients (age 26–52 showing p = 0.0025 and age 22–46 showing p = 0.001, respectively).…”

“…Interestingly, they found a significant association between methylated LINC00299 levels and TNBC subgroup in young age patients (age 26–52 showing p = 0.0025 and age 22–46 showing p = 0.001, respectively). These results suggest a potential role of hypermethylated LINC00299 as diagnostic biomarker in young women with TNBC [ 94 ].…”

Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications

“…For instance, a prospective study on miRNA gene methylation suggests that there are five differentially methylated miRNA genes in PB of patients before a diagnosis of BC, indicating that the abnormal methylation of miRNA genes may be an event before BC initiation and differential methylation of miRNA genes can be used as risk biomarkers for BC [ 134 ]. Furthermore, another prospective study using digital PCR to detect DNA in PB leukocytes shows that hypermethylation of the LINC00299 gene is an effective biomarker of TNBC in young women [ 135 ]. These findings shed light on the fact that the methylation pattern of ncRNAs can be used as a molecular diagnostic marker of BC.…”