Journal Article

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

Han, Junsong, Chan, Tianlong, Wang, Ke, Xu, Yichun, Zhang, Congmeng, Bi, Ling, Su, Jun, Qin, Xiong, Zhou, Jiajing, Wang, Yichao, Gong, Yi, Wu, Guanjin, Gu, Yifeng, Yang, Yong

2023

Overview

Background Lung 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. Methods This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. Results This 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. Conclusions This 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adenocarcinoma of Lung - diagnosis / Adenocarcinoma of Lung - genetics / Analysis / Atrophy / Biological markers / Biomarkers / Biomedical and Life Sciences / Biomedicine / Care and treatment / Cell-free mtDNA / Cell-Free Nucleic Acids / Cellular Metabolism Therapy / Development and progression / Diagnosis / DNA methylation / DNA, Mitochondrial - genetics / Early Detection of Cancer / Gene mutations / Genetic aspects / Genome, Mitochondrial - genetics / Genomes / Genomics / Health aspects / High-throughput screening (Biochemical assaying) / Humans / Lung adenocarcinoma / Lung cancer / Lung Neoplasms - diagnosis / Lung Neoplasms - genetics / Medicine/Public Health / Methods / Mitochondria / Mitochondrial DNA / Morbidity / Mutation / Mutations