Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA‐based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer‐free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR‐21‐5p (3′ addition C), miR‐23a‐3p and tRF‐Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early‐stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF‐7 and MDA‐MB‐231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.

Background MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer.

The telomere G‐tail (G‐tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G‐tail length of breast cancer (BC) patients and cancer‐free individuals and evaluated the association between the G‐tail length and the presence of BC. A significant shortening of the median G‐tail length was observed in BC patients compared with cancer‐free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G‐tail length might be a potential biomarker for BC detection.

Genome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations conferred by this SNP have not been described. We genotyped SNP rs6817105 and examined the relationships among rs6817105 genotype, clinical characteristics, echocardiographic parameters, and electrophysiological parameters in 574 AF patients and 1,554 non-AF controls. Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor allele frequency was significantly higher in AF patients than non-AF controls (66% vs. 47%, odds ratio 2.12, p = 4.9 × 10−26). Corrected sinus node recovery time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557 ± 315 ms, CT 486 ± 273 ms, TT 447 ± 234 ms, p = 0.001; LAVI: CC 43.6 ± 12.1, CT 42.4 ± 13.6, TT 39.8 ± 11.6, p = 0.030). There were no significant differences between rs6817105 genotype and the serum concentrations of miRNAs. These findings strongly implicate rs6817105 minor allele in sinus node dysfunction and left atrial enlargement.

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Background The telomere G-tail, located at the terminal 3’-end, plays an important role in the maintenance of chromosome stability. Telomere G-tail length has been shown to be related to the presence of various cancers; however, the association between telomere G-tail length and breast cancer has remained unclear. Methods We measured the length of the leukocyte telomere G-tail using the hybridization protection assay, which has the advantages of being simple to perform, accurate and highly sensitive for G-tails as short as 20 nucleotides. The association between telomere G-tail length and presence of breast cancer was estimated by comparing breast cancer patients (n=70) and cancer-free individuals (n=83). We recruited cStage I-III breast cancer patients who underwent surgery between November 2016 and December 2017 at Hiroshima University Hospital. Cancer-free individuals included age-matched female individuals with no previous or current history of any cancer. Results The median telomere G-tail length was significantly shorter in breast cancer patients (11,886.70 ± 2,008.74 RLU/μg DNA) than in cancer-free individuals (13,336.00 ± 2,072.31 RLU/μg DNA; p < 0.01). Shortening of the telomere G-tail length was observed in the phase of ductal carcinoma in situ, and this trend was observed with or without shortening of the total telomere length. Spearman’s rank correlation analysis showed that there was no significant association between telomere G-tail length and total telomere length in breast cancer patients (ρ = -0.09; p = 0.48). In contrast, a significant correlation was found between telomere G-tail length and total telomere length in cancer-free individuals (ρ = 0.29; p = 0.01). Conclusions Our study indicated that leukocyte telomere G-tail length may serve as a novel potential biomarker for detection of breast cancer. Citation Format: Yumiko Koi, Yasuhiro Tsutani, Yukie Nishiyama, Shinsuke Sasada, Norio Masumoto, Takayuki Kadoya, Ryou-u Takahashi, Morihito Okada, Hidetoshi Tahara. Telomere G-tail length correlates with the presence of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-04-01.

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