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Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non‐TNBC) accounts for 80–90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA‐derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high‐throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non‐TNBC. Furthermore, quantitative reverse‐transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR‐7816, tDR‐5334, and tDR‐4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR‐7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR‐7816 expression as a novel potential biomarker for the diagnosis of patients with early non‐TNBC. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia‐treated TNBC cell lines through the use of high‐throughput sequencing technique. Quantitative real‐time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR‐0009 [derived from transfer RNA (tRNA)Gly‐GCC‐1‐1] and tDR‐7336 (derived from tRNA Gly‐GCC‐1–2) were significantly upregulated when the SUM‐1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)‐6, which may be the underlying mechanism of hypoxia‐induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein–protein interaction network for predicted target genes established by the STRING database manifested that tDR‐0009 (tDR‐7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. Triple negative breast cancer (TNBC) is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. We provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. [ABSTRACT FROM AUTHOR]