Evidence map›Paper›PMID 42063110›Full record

ArticleGenome medicine2026

Integrative multi-omics profiling reveals distinct evolutionary and immunogenic features of brain oligometastasis in lung adenocarcinoma.

Rongxin Liao, Qian Yu, Yusheng Huang, Hengqiu He, Mengmeng Song, Xuan Gao, Lu Shen, Yihao Tao, Lin Li, Gang Xiao and 8 more

Abstract read
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Rongxin Liao *Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Qian Yu *Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Yusheng Huang *Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Hengqiu HeDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Mengmeng SongGeneplus-Beijing, Beijing, 100101, China.
Xuan GaoGeneplus-Beijing, Beijing, 100101, China.
Lu ShenGeneplus-Beijing, Beijing, 100101, China.
Yihao TaoDepartment of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Lin LiDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400000, China.
Gang XiaoDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Rui KongDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Cancan WangDepartment of Pathology, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang, 830000, China.
Shunping HuangDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Xiaoyue ZhangDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Zaicheng XuDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Rongrong ZhouDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. zhourr@csu.edu.cn.
Zhenzhou YangDepartment of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. yangzz@cqmu.edu.cn.
Yuan Peng *Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. pengyuan1127@cqmu.edu.cn.

Funding

Natural Science Foundation of China 82573031Program for Youth Innovation in Future Medicine of Chongqing Medical University W0172the China Postdoctoral Science Foundation 2022M710555the National Natural Science Foundation of China 82273572
6 · The paper itself

Abstract

backgroundEmerging evidence has demonstrated that lung cancer patients with brain oligometastases (oligo-BMs) could benefit from local radical therapies. Despite rapid advancements in the treatment of oligometastatic disease, the molecular determinants governing the oligometastatic phenotype in the central nervous system remain elusive.

methodsWe performed 1021-panel sequencing, transcriptome profiling, DNA methylation mapping, and multiplex immunohistochemistry on 20 paired primary lung adenocarcinoma and oligo-BMs specimens to delineate their evolutionary dynamics and microenvironmental characteristics.

resultsA pronounced intertumor heterogeneity was observed between primary tumors (PTs) and oligo-BMs, while intratumoral heterogeneity was conserved across lesions. Subclonal analysis and phylogenetic reconstruction demonstrated that oligo-BMs exhibited predominant polyclonal seeding patterns and parallel progression trajectories. Moreover, oligo-BMs displayed a more immunosuppressed microenvironment compared to PTs, characterized by attenuated immunogenic cell death signatures, downregulation of immune-activated pathways, and diminished infiltration of activated immune cells (including B cells, NK cells, and Th1 cells). The methylation levels at functional genomic regions were highly concordant between PTs and oligo-BMs. Notably, we identified NLGN1 as a potential regulator of oligo-BM, where the hypermethylation at its genebody regions was mechanistically associated with transcriptional upregulation. Clinical validation revealed that NLGN1 was specifically overexpressed in BMs compared to PTs and extracranial metastases, correlating with advanced pathological stages and poor prognosis. In vivo studies further confirmed NLGN1 promotes BM in mice.

conclusionsOur findings provide novel insights into the evolutionary trajectory, immune landscape and methylation pattern of oligo-BMs, potentially paving the way for the development of innovative therapeutic strategies for lung cancer patients with oligo-BMs.

Indexed as

Adenocarcinoma of LungBrain NeoplasmsLung NeoplasmsAnimalsDNA MethylationEvolution, MolecularFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMiddle AgedMultiomicsTumor MicroenvironmentBrain oligometastasisEvolutionary dynamicsLUADMicroenvironmental characteristicsNLGN1

Identifiers

PMID42063110
PMCPMC13248418

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.