Journal Article

Characterization of the genomic landscape in liver oligometastatic NSCLC

Xu, Zaicheng, Huang, Shunping, Zhang, Xiaoyue, Peng, Yuan, Xiao, Xiao, Yi, Guangming, Tang, Hongjun, Yang, Zhenzhou, Liao, Rongxin, Zeng, Chuan, Liu, Liangzhong, Shen, Lu

2025

Overview

Objectives Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC. Methods Paired liver metastatic tissue samples and peripheral blood from 32 liver oligometastatic NSCLC patients were concurrently collected for comprehensive genomic analysis using next-generation sequencing. Results A total of 206 mutated genes in 32 patients were detected, with a median of 4 mutations per sample. The most frequent alterations (> 10%) in liver oligometastasis were TP53 (72%), EGFR (50%), RB1 (19%) and SMARCA4 (12%). The co-occurrence rate of TP53 and RB1 in our cohort was significantly higher than that in the TCGA-LUAD cohort. Age, APOBEC, homologous recombination deficiency (HRD) and deficient mismatch repair (dMMR) established the mutational signature of liver oligometastatic NSCLC. The median tumor mutation burden (TMB) was 4.8 mutations/Mb. A total of 78.12% patients harbored at least one potentially actionable molecular alteration that may guide further targeted therapy according to the OncoKB evidence. Conclusions Our study comprehensively delineated the genomic characteristics of liver oligometastatic NSCLC - such findings were helpful to better understand the distinct clinic-biological features of oligometastasis and optimize personalized treatment of this population.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Analysis / Biomarkers / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - pathology / Care and treatment / Development and progression / Diagnosis / DNA Helicases / DNA sequencing / FDA approval / Female / Gene mutations / Genes / Genetic aspects / Genomes / Genomic analysis / Genomic profiling / Genomics - methods / Health aspects / Health Promotion and Disease Prevention / Hepatocytes / High-Throughput Nucleotide Sequencing / Homologous recombination / Humans / Immunotherapy / Liver / Liver cancer / Liver Neoplasms - genetics / Liver Neoplasms - secondary / Liver oligometastasis / Lung cancer / Lung cancer, Non-small cell / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Male / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Middle Aged / Mismatch repair / Mutation / Next-generation sequencing / Non-small cell lung carcinoma / NSCLC / Nuclear Proteins / Nucleotide sequencing / Oncology / p53 Protein / Patients / Peripheral blood / Population studies / Prognosis / Retinoblastoma Binding Proteins - genetics / Small cell lung carcinoma / Software / Statistical analysis / Surgical Oncology / Tomography / Transcription Factors / Tumor mutational burden / Tumor Suppressor Protein p53 - genetics / Tumors / Ubiquitin-Protein Ligases