Gao Zitong, Jijiwa Mayumi, Nasu Masaki, Borgard Heather, Gong Ting, Xu Jinwen, Chen Shaoqiu, Fu Yuanyuan, Chen Yu, Hu Xiamin, Huang Gang, Deng Youping
Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Molecular Biosciences and Bioengineering Program, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Mol Ther Oncolytics. 2022 Jul 6;26:207-225. doi: 10.1016/j.omto.2022.07.002. eCollection 2022 Sep 15.
Transfer RNA (tRNA)-derived fragment (tRDF) is a novel small non-coding RNA that presents in different types of cancer. The comprehensive understanding of tRDFs in non-small cell lung cancer remains largely unknown. In this study, 1,550 patient samples of non-small cell lung cancer (NSCLC) were included, and 52 tRDFs with four subtypes were identified. Six tRDFs were picked as diagnostic signatures based on the tRDFs expression patterns, and area under the curve (AUC) in independent validations is up to 0.90. Two signatures were validated successfully in plasma samples, and six signatures confirmed the consistency of distinguished expression in NSCLC cell lines. Ten tRDFs along with independent risk scores can be used to predict survival outcomes by stages; 5a_tRF-Ile-AAT/GAT can be a prognosis biomarker for early stage. Association analysis of tRDFs-signatures-correlated mRNAs and microRNA (miRNA) were targeted to the cell cycle and oocyte meiosis signaling pathways. Five tRDFs were assessed to associate with PD-L1 immune checkpoint and correlated with the genes that target in PD-L1 checkpoint signaling pathway. Our study is the first to provide a comprehensive analysis of tRDFs in lung cancer, including four subtypes of tRDFs, investigating the diagnostic and prognostic values, and demonstrated their biological function and transcriptional role as well as potential immune therapeutic value.
转运RNA（tRNA）衍生片段（tRDF）是一种新型的小非编码RNA，存在于不同类型的癌症中。目前，对于非小细胞肺癌中tRDF的全面了解仍非常有限。本研究纳入了1550例非小细胞肺癌（NSCLC）患者样本，鉴定出了52种具有四种亚型的tRDF。基于tRDF的表达模式，挑选出6种tRDF作为诊断标志物，其在独立验证中的曲线下面积（AUC）高达0.90。其中两种标志物在血浆样本中得到成功验证，六种标志物证实了在NSCLC细胞系中差异表达的一致性。10种tRDF以及独立风险评分可用于按阶段预测生存结果；5a_tRF-Ile-AAT/GAT可作为早期阶段的预后生物标志物。对与tRDF标志物相关的mRNA和微小RNA（miRNA）进行关联分析，发现其靶向细胞周期和卵母细胞减数分裂信号通路。评估发现5种tRDF与PD-L1免疫检查点相关，并与PD-L1检查点信号通路中的靶向基因相关。我们的研究首次对肺癌中的tRDF进行了全面分析，包括tRDF的四种亚型，研究了其诊断和预后价值，并展示了它们的生物学功能、转录作用以及潜在的免疫治疗价值。
