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转移性非小细胞肺癌中肿瘤非整倍体的临床和分子相关性。

Clinical and molecular correlates of tumor aneuploidy in metastatic non-small cell lung cancer.

机构信息

Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.

Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.

出版信息

Sci Rep. 2024 Aug 21;14(1):19375. doi: 10.1038/s41598-024-66062-5.

DOI:10.1038/s41598-024-66062-5
PMID:39169079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11339421/
Abstract

Recent studies have linked elevated tumor aneuploidy to anti-tumor immune suppression and adverse survival following immunotherapy. Herein, we provide supportive evidence for tumor aneuploidy as a biomarker of response to immunotherapy in patients with non-small cell lung cancer (NSCLC). We identify a dose-response relationship between aneuploidy score and patient outcomes. In two independent NSCLC cohorts (n = 659 patients), we demonstrate a novel association between elevated aneuploidy and non-smoking-associated oncogenic driver mutations. Lastly, we report enrichment of TERT amplification and immune-suppressive phenotypes of highly aneuploid NSCLC. Taken together, our findings emphasize a potentially critical role for tumor aneuploidy in guiding immunotherapy treatment strategies.

摘要

最近的研究将肿瘤非整倍性与抗肿瘤免疫抑制和免疫治疗后的不良生存联系起来。在此，我们为肿瘤非整倍性作为非小细胞肺癌（NSCLC）患者免疫治疗反应的生物标志物提供了支持性证据。我们确定了非整倍性评分与患者结局之间的剂量反应关系。在两个独立的 NSCLC 队列（n=659 名患者）中，我们证明了非整倍性升高与非吸烟相关的致癌驱动基因突变之间存在新的关联。最后，我们报告了 TERT 扩增和高度非整倍体 NSCLC 的免疫抑制表型富集。总之，我们的发现强调了肿瘤非整倍性在指导免疫治疗策略方面的潜在关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/f6f90627263f/41598_2024_66062_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/26f3ed303f10/41598_2024_66062_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/7ac6d89619f5/41598_2024_66062_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/f6f90627263f/41598_2024_66062_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/26f3ed303f10/41598_2024_66062_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/7ac6d89619f5/41598_2024_66062_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ef/11339421/f6f90627263f/41598_2024_66062_Fig3_HTML.jpg

相似文献

[1]
Clinical and molecular correlates of tumor aneuploidy in metastatic non-small cell lung cancer.

Sci Rep. 2024-8-21

[2]
Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis.

JAMA Netw Open. 2019-7-3

[3]
ZFHX3 mutation as a protective biomarker for immune checkpoint blockade in non-small cell lung cancer.

Cancer Immunol Immunother. 2021-1

[4]
Integration of comprehensive genomic profiling, tumor mutational burden, and PD-L1 expression to identify novel biomarkers of immunotherapy in non-small cell lung cancer.

Cancer Med. 2021-4

[5]
Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

Anticancer Res. 2024-5

[6]
Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer.

J Immunother Cancer. 2020-2

[7]
BRAF mutations and BRAF mutation functional class have no negative impact on the clinical outcome of advanced NSCLC and associate with susceptibility to immunotherapy.

Eur J Cancer. 2021-5

[8]
Driver gene alterations profiling of Chinese non-small cell lung cancer and the effects of co-occurring alterations on immunotherapy.

Cancer Med. 2021-10

[9]
Response to Checkpoint Inhibition in Non-Small Cell Lung Cancer with Molecular Driver Alterations.

Oncol Res Treat. 2020-4-8

[10]
Relationship between the efficacy of immunotherapy and characteristics of specific tumor mutation genes in non-small cell lung cancer patients.

Thorac Cancer. 2020-6

引用本文的文献

[1]
Tumor aneuploidy as a prognostic and predictive biomarker in immune checkpoint blockade.

Nat Genet. 2025-6-30

[2]
Updates on radiotherapy-immunotherapy combinations: Proceedings of 8th Annual ImmunoRad Conference.

Oncoimmunology. 2025-12

本文引用的文献

[1]
The regulations of telomerase reverse transcriptase (TERT) in cancer.

Cell Death Dis. 2024-1-26

[2]
Exploiting tumor aneuploidy as a biomarker and therapeutic target in patients treated with immune checkpoint blockade.

NPJ Precis Oncol. 2024-1-2

[3]
Letter to the Editor: Reply to Kus and Aktas.

J Thorac Oncol. 2023-8

[4]
Oncogene-like addiction to aneuploidy in human cancers.

Science. 2023-8-25

[5]
Cancer aneuploidies are shaped primarily by effects on tumour fitness.

Nature. 2023-7

[6]
Optimizing cancer immunotherapy response prediction by tumor aneuploidy score and fraction of copy number alterations.

NPJ Precis Oncol. 2023-6-3

[7]
Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer.

Nat Genet. 2023-5

[8]
Tumor aneuploidy predicts survival following immunotherapy across multiple cancers.

Nat Genet. 2022-12

[9]
Highly aneuploid non-small cell lung cancer shows enhanced responsiveness to concurrent radiation and immune checkpoint blockade.

Nat Cancer. 2022-12

[10]
Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

JAMA Netw Open. 2022-5-2

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