Mitochondria-derived small RNAs as diagnostic biomarkers in lung cancer patients through a novel ratio-based expression analysis methodology

Zongtao Yu; Shaoqiu Chen; Zhenming Tang; Ying Tang; Zhougui Ling; Hongwei Wang; Ting Gong; Zitong Gao; Gehan Devendra; Gang Huang; Wei Chen; Youping Deng

doi:10.1016/j.gendis.2022.07.013

Mitochondria-derived small RNAs as diagnostic biomarkers in lung cancer patients through a novel ratio-based expression analysis methodology

Genes Dis. 2022 Aug 7;10(3):1055-1061. doi: 10.1016/j.gendis.2022.07.013. eCollection 2023 May.

Authors

Zongtao Yu^{1

2}, Shaoqiu Chen^{3

4}, Zhenming Tang⁵, Ying Tang⁵, Zhougui Ling⁵, Hongwei Wang⁶, Ting Gong^{3

4}, Zitong Gao^{3

4}, Gehan Devendra^{3

7}, Gang Huang⁸, Wei Chen⁹, Youping Deng³

Affiliations

¹ Department of Laboratory Medicine, Affiliated Taihe Hospital of Xi'an Jiaotong University Health Science Center, Shiyan, Hubei 710061, China.
² Department of Internal Medicine, Rush University Cancer Center, Rush University Medical Center, Kidston House, Chicago, IL 60612, USA.
³ Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
⁴ Molecular Biosciences and Bioengineering Program, College of Tropical Agriculture and Human Resources, The University of Hawaii at Manoa, Honolulu, HI 96822, USA.
⁵ Department of Pulmonary and Critical Care Medicine, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, China.
⁶ Division of Research and Development, Decoding Therapeutics Corp, Mt Prospect, IL 60056, USA.
⁷ Division Chief Pulmonary & Critical Care Medicine, The Queen's Medical Center, John A Burns School of Medicine, Honolulu, HI 96813, USA.
⁸ Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
⁹ Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Abstract

Small non-coding RNAs are potential diagnostic biomarkers for lung cancer. Mitochondria-derived small RNA (mtRNA) is a novel regulatory small non-coding RNA that only recently has been identified and cataloged. Currently, there are no reports of studies of mtRNA in human lung cancer. Currently, normalization methods are unstable, and they often fail to identify differentially expressed small non-coding RNAs (sncRNAs). In order to identify reliable biomarkers for lung cancer screening, we used a ratio-based method using mtRNAs newly discovered in human peripheral blood mononuclear cells. In the discovery cohort (AUC = 0.981) and independent validation cohort (AUC = 0.916) the prediction model of eight mtRNA ratios distinguished lung cancer patients from controls. The prediction model will provide reliable biomarkers that will allow blood-based screening to become more feasible and will help make lung cancer diagnosis more accurate in clinical practice.

Keywords: Lung cancer; Mitochondria-derived small RNAs; Plasma; Ratio; Small non-coding RNAs.

Grants and funding

P20 GM103466/GM/NIGMS NIH HHS/United States