Identification of tRNA-derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple-negative breast cancer

Wanting Feng; Yongfei Li; Jiahui Chu; Jun Li; Yanhong Zhang; Xiaorong Ding; Ziyi Fu; Wei Li; Xiang Huang; Yongmei Yin

doi:10.1002/cam4.1761

Identification of tRNA-derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple-negative breast cancer

Cancer Med. 2018 Oct;7(10):5130-5144. doi: 10.1002/cam4.1761. Epub 2018 Sep 21.

Authors

Wanting Feng^{1

2}, Yongfei Li¹, Jiahui Chu^{1

3}, Jun Li¹, Yanhong Zhang¹, Xiaorong Ding^{1

2}, Ziyi Fu^{1

4}, Wei Li¹, Xiang Huang¹, Yongmei Yin¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Oncology, The Affiliated Huaian NO. 1 People's Hospital of Nanjing Medical University, Huaian, China.
³ Department of Pulmonary and Critical Care Medicine, Fuzhou General Hospital, Fuzhou, China.
⁴ Nanjing Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Abstract

Triple-negative breast cancer (TNBC), an intrinsic subtype of breast cancer, is characterized by aggressive pathology and shorter overall survival. Yet there is no effective therapy for these patients. Breast cancer stem cells (BCSCs) in TNBC may account for treatment failure. It is urgent to identify new therapeutic targets for TNBC. tRNA-derived small noncoding RNAs (tDRs) represent a new class of small noncoding RNAs (sncRNA), which have been reported in some human diseases and biological processes. However, there is no detailed information about the relationship between tDRs and BCSCs. In this study, a population of CD44⁺ /CD24^-/low cells was isolated and identified by reliable BCSC surface markers. tDR expression profiles in TNBC and non-TNBC CSCs were performed by RNA sequencing. A total of 1327 differentially expressed tDRs contained 18 upregulated and 54 downregulated in TNBC group. Furthermore, the selected tDRs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). tDR-000620 expression level was consistently lower in TNBC cell lines CSCs (all P < 0.05) and serum samples (t = 2.597, P = 0.013). tDR-000620 expression was significant association with age (P = 0.018), node status (P = 0.026) and local recurrence (P = 0.019) by chi-square test. Kaplan-Meier method with log-rank test for comparison of recurrence curves. The results showed that the tDR-000620 expression (P = 0.002) and node status (P = 0.001) group were statistically significant with recurrence-free survival. Furthermore, multivariate Cox regression demonstrated that lymphatic metastasis (HR, 3.616; 95% CI, 1.234-10.596; P = 0.019) and low tDR-000620 expression (HR, 0.265; 95% CI, 0.073-0.959; P = 0.043) were two independent adverse predictive factors for recurrence-free survival. Finally, we found that tDR-000620 participated in some important biological processes though GO and KEGG analysis. Taken together, our study reveals the expression profiles of tDRs in TNBC and non-TNBC CSCs. It offers helpful information to understand the tDR-000620 expression is responsible for the aggressive phenotype of BCSCs. It may provide predictive biomarkers and therapeutic targets for TNBC recurrence.

Keywords: biomarker; stem cells; tDRs; triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Biomarkers, Tumor / genetics
Cell Line, Tumor
Female
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis / genetics
MCF-7 Cells
Neoplasm Recurrence, Local / genetics*
Neoplastic Stem Cells / chemistry*
RNA, Small Untranslated / genetics*
RNA, Transfer / genetics*
Sequence Analysis, RNA / methods
Triple Negative Breast Neoplasms / genetics*

Substances

Biomarkers, Tumor
RNA, Small Untranslated
RNA, Transfer