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.
We compared the surgical outcomes between 114 patients who did not receive neoadjuvant therapy (group 1) and 92 others who received neoadjuvant chemoradiotherapy (nCRT) (group 2), and assessed the preoperative and surgical factors that influence postoperative morbidity to determine the impact of nCRT on morbidity and mortality after esophagectomy via cervical, right transthoracic, and abdominal approaches. The overall postoperative morbidity rates were 44.7% and 55.4% in groups 1 and 2, respectively (P = 0.13). Rates of anastomotic leak (8.8% vs. 16.3%; P = 0.10), pneumonia (9.6% vs. 13.0%; P = 0.44), recurrent nerve palsy (15.8% vs. 10.9%; P = 0.31), and all other complications did not significantly differ between the groups. Multivariable analysis revealed cervical lymph node dissection (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.01-3.84; P = 0.047) as the sole independent covariate for overall morbidity. Furthermore, a history of cardiovascular disease (OR, 2.90; 95% CI, 1.03-8.24; P = 0.045), the retrosternal reconstruction route (OR, 15.15; 95% CI, 3.56-62.50; P = 0.0002), and a longer surgical duration (OR, 1.01; 95% CI, 1.002-1.02; P = 0.01) were independent covariates for anastomotic leakage, and advanced age (OR, 1.08; 95% CI, 1.01-1.15; P = 0.02) and lower body mass index (OR, 1.16; 95% CI, 1.01-1.33; P = 0.04) were independent covariates for pneumonia. However, whether or not patients received nCRT was irrelevant. We found that nCRT is safe for three-incision esophagectomy and it does not increase the incidence of postoperative morbidity and mortality relative to esophagectomy alone.
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