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Open AccessArticle

Interplay of tRNA-Derived Fragments and T Cell Activation in Breast Cancer Patient Survival

1
Center for Statistical Science, Department of Industrial Engineering, Tsinghua University, Beijing 100084, China
2
Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520, USA
3
SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
4
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China
5
Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT 06520, USA
6
Department of Mathematical Sciences, University of Nevada, Las Vegas, NV 89154, USA
7
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06520, USA
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(8), 2230; https://doi.org/10.3390/cancers12082230
Received: 6 July 2020 / Revised: 28 July 2020 / Accepted: 7 August 2020 / Published: 10 August 2020
Effector CD8+ T cell activation and its cytotoxic function are positively correlated with improved survival in breast cancer. tRNA-derived fragments (tRFs) have recently been found to be involved in gene regulation in cancer progression. However, it is unclear how interactions between expression of tRFs and T cell activation affect breast cancer patient survival. We used Kaplan–Meier survival and multivariate Cox regression models to evaluate the effect of interactions between expression of tRFs and T cell activation on survival in 1081 breast cancer patients. Spearman correlation analysis and weighted gene co-expression network analysis were conducted to identify genes and pathways that were associated with tRFs. tRFdb-5024a, 5P_tRNA-Leu-CAA-4-1, and ts-49 were positively associated with overall survival, while ts-34 and ts-58 were negatively associated with overall survival. Significant interactions were detected between T cell activation and ts-34 and ts-49. In the T cell exhaustion group, patients with a low level of ts-34 or a high level of ts-49 showed improved survival. In contrast, there was no significant difference in the activation group. Breast cancer related pathways were identified for the five tRFs. In conclusion, the identified five tRFs associated with overall survival may serve as therapeutic targets and improve immunotherapy in breast cancer. View Full-Text
Keywords: breast cancer; T cell activation score; tRNA-derived fragments; pathway enrichment analysis; cancer survival breast cancer; T cell activation score; tRNA-derived fragments; pathway enrichment analysis; cancer survival
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MDPI and ACS Style

Shan, N.; Li, N.; Dai, Q.; Hou, L.; Yan, X.; Amei, A.; Lu, L.; Wang, Z. Interplay of tRNA-Derived Fragments and T Cell Activation in Breast Cancer Patient Survival. Cancers 2020, 12, 2230.

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