Comprehensive landscape of tRNA-derived fragments in lung cancer
Zitong Gao1,2,3, Mayumi Jijiwa1, Masaki Nasu1
1Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Abstract:
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.
Insights
Transfer RNA (tRNA)-derived fragments (tRDFs) show promise as biomarkers for non-small cell lung cancer (NSCLC). This study identified diagnostic and prognostic tRDF signatures, revealing their potential in early detection and therapeutic strategies.
Area of Science:
- Molecular Biology
- Oncology
- Genomics
Background:
- Transfer RNA (tRNA)-derived fragments (tRDFs) are emerging as significant small non-coding RNAs implicated in various cancers.
- The role and diagnostic potential of tRDFs in non-small cell lung cancer (NSCLC) remain largely unexplored.
Purpose of the Study:
- To comprehensively analyze tRDFs in NSCLC, identify diagnostic and prognostic biomarkers, and explore their biological functions and therapeutic potential.
Main Methods:
- Analysis of 1,550 NSCLC patient samples to identify and characterize tRDFs.
- Development and validation of tRDF-based diagnostic signatures using expression patterns and Area Under the Curve (AUC).
- Assessment of tRDFs for prognostic value, association with mRNA/miRNA, and correlation with PD-L1 immune checkpoint.
Main Results:
- Identified 52 tRDFs across four subtypes in NSCLC.
- Developed six tRDF diagnostic signatures with AUC up to 0.90, validated in plasma and cell lines.
- Ten tRDFs demonstrated prognostic value for survival outcomes, with one biomarker for early-stage prognosis.
- tRDFs were linked to cell cycle, oocyte meiosis pathways, and PD-L1 immune checkpoint signaling.
Conclusions:
- This study provides the first comprehensive analysis of tRDFs in lung cancer, establishing their diagnostic and prognostic utility.
- Identified tRDF signatures hold potential as biomarkers for NSCLC diagnosis, prognosis, and immune therapeutic strategies.
- tRDFs play roles in key cellular pathways and immune checkpoint regulation, offering new avenues for cancer research.
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