Abstract 1241: Six potential biomarkers for non-small cell lung cancer diagnosis and prognosis
Authors: Gao Zitong , Jijiwa Mayumi , Nasu Masaki , Borgard Heather , Xu Jinwen , Gong Ting , Chen Shaoqiu , Fu Yuanyuan , Deng Youping 
Published: June 2022

tRNA-derived fragment (tRDF) is novel small non-coding RNA that presences in different types of cancer tissue. More evidence has shown that tRDFs are associated with cancer progression through cell proliferation. In this study, we took advantage of public database and small RNA sequencing to investigate the diagnosis and prognosis potential of tRDFs as a biomarker for non-small cell lung cancer. We collected 1028 patient samples including adenocarcinoma from TCGA, GEO, and plasma. We gathered all fragments upstream sequences and 5’-tRF, to be categorized as 5’-tRDF and fragments 3’-tRF and downstream sequences, to be categorized as 3’-tRDF. 52 tRDFs were identified that were common in TCGA and GEO, and clustering results separated two GEO with TCGA as distinct expression pattern. 11 differentially expressed tRDFs were screened out from the GEO data and exhibited excellent diagnostic value. The AUC of two independent validations was up to 0.90. Six tRDFs, 5P_tRNA-Gly-TCC-1-1, 5a_tRF-Ile-AAT/GAT, 3P_tRNA-Arg-TCG-1-1, and 3P_tRNA-Arg-TCT-4-1, 5P_tRNA-Asn-GTT-2-3, 5a_tRF-Asp-GTC, were named as tRDF signatures and exhibited the same excellent diagnosis ability, and combination had better performance than individual tRDFs. Plasma data validated the diagnostic characteristics of two signatures, 3P_tRNA-Arg-TCG-1-1 and 5P_tRNA-Asn-GTT-2-3, that could serve as novel diagnostic biomarkers. We investigated the relationship between signatures and prognosis by stages and following-up times in TCGA-LUAD. 5a_tRF-Ile-AAT/GAT were identified to be a significant prognostic value with survival time on 36 months and 24 months among early stages patients. 3P_tRNA-Arg-TCT-4-1 was identified to associate with survival outcome within 12 and six months in early stages. We also assessed the role of tRDFs in transcriptional and post-transcriptional events. 3’-tRDFs showed more correlation with miRNA than 5’-tRDFs. A correlation analysis showed signatures, 5a_tRF-Asp-GTC, dominated the most correlation with miRNAs. Enrichment results of six tRDFs signatures presented PI3K-Akt, MAPK, and endocytosis signaling pathways are associated with tRDF target miRNAs. We also analyzed the signaling pathway characteristic of the six signatures tRDFs-target genes and found the tRDFs correlated genes are significantly activated in the cell cycle, oocyte meiosiss. Five signatures were assessed to associate with PD-L1 immune checkpoint and correlated with the genes that targets in PD-L1 checkpoint signaling pathway. Our study is the first to provide a comprehensive analysis of tRDFs as biomarkers in lung cancer, investigating the diagnostic and prognostic values of tRDFs, and demonstrated their biological function and transcriptional role as well as potential immune therapeutic value. This work highlights the potential clinical utility of tRDFs in lung cancer therapy and provides evidence of tRDF-target treatment in lung cancer.

Citation Format: Zitong Gao, Mayumi Jijiwa, Masaki Nasu, Heather Borgard, Jinwen Xu, Ting Gong, Shaoqiu Chen, Yuanyuan Fu, Youping Deng. Six potential biomarkers for non-small cell lung cancer diagnosis and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1241.