Molecular fingerprints of nuclear genome and mitochondrial genome for early diagnosis of lung adenocarcinoma

Journal of Translational Medicine

卷:21

Research

Ke Wang¹  Congmeng Zhang²  Yichao Wang²  Yifeng Gu²  Guanjin Wu²  Ling Bi³  Xiong Qin⁴  Yong Yang⁴  Tianlong Chan⁵  Jiajing Zhou⁵  Yichun Xu⁶  Yi Gong⁶  Jun Su⁶  Junsong Han⁶ 

[1] Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China;

[2] Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110, Ganhe Road, Shanghai, China;

[3] Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110, Ganhe Road, Shanghai, China;Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China;

[4] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, No.241, Huaihai West Road, Shanghai, China;

[5] National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, No.151, Libing Road, 201203, Shanghai, China;

[6] National Engineering Research Center for Biochip at Shanghai and Shanghai Biochip Limited Corporation, No.151, Libing Road, 201203, Shanghai, China;Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai, China;

关键词: Lung adenocarcinoma;    Cell-free mtDNA;    Mutations;    Diagnosis;   

DOI  :  10.1186/s12967-023-04099-2

 received in 2023-01-08, accepted in 2023-03-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis.MethodsThis observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed.ResultsThis study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD.ConclusionsThis study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.

【 授权许可】

CC BY   
© The Author(s) 2023. corrected publication 2023

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