Plasma tRNA-derived small RNAs signature as a predictive and prognostic biomarker in lung adenocarcinoma

Jun Wang; Xianyu Liu; Weifang Cui; Qun Xie; Wei Peng; Heng Zhang; Yang Gao; Chunfang Zhang; Chaojun Duan

doi:10.1186/s12935-022-02481-6

Plasma tRNA-derived small RNAs signature as a predictive and prognostic biomarker in lung adenocarcinoma

Cancer Cell Int. 2022 Feb 3;22(1):59. doi: 10.1186/s12935-022-02481-6.

Authors

Jun Wang^{1

2

3}, Xianyu Liu^{1

2

3}, Weifang Cui^{1

2

3}, Qun Xie⁴, Wei Peng⁵, Heng Zhang^{1

2

6}, Yang Gao^{1

2

6}, Chunfang Zhang^{1

2

6}, Chaojun Duan^{7

8

9

10

11}

Affiliations

¹ Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
² Hunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, 410008, Hunan, People's Republic of China.
³ Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
⁴ Department of Ultrasonic Imaging, Affiliated Hospital of Hunan Traditional Chinese Medicine Research Institute, Changsha, 410006, Hunan, People's Republic of China.
⁵ Department of Oncology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, 410006, Hunan, People's Republic of China.
⁶ Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
⁷ Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. duancjxy@csu.edu.cn.
⁸ Hunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, 410008, Hunan, People's Republic of China. duancjxy@csu.edu.cn.
⁹ Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. duancjxy@csu.edu.cn.
¹⁰ Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. duancjxy@csu.edu.cn.
¹¹ National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, People's Republic of China. duancjxy@csu.edu.cn.

Abstract

Background: The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers.

Methods: tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines.

Results: A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs' expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines.

Conclusion: These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery.

Keywords: Diagnostic biomarker; Lung adenocarcinoma; Network; tRFs; tsRNAs.