Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma.

IF 9.4 1区医学 Q1 HEMATOLOGY

Experimental Hematology & Oncology Pub Date : 2024-10-28 DOI:10.1186/s40164-024-00574-8

Fanjie Meng, Hao Li, Ruoyi Jin, Airong Yang, Hao Luo, Xiao Li, Peiyu Wang, Yaxing Zhao, Olga Chervova, Kaicheng Tang, Sida Cheng, Bin Hu, Yun Li, Jianpeng Sheng, Fan Yang, David Carbone, Kezhong Chen, Jun Wang

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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD.

Methods: We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently.

Results: Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p < 0.05), compared to LN negative tumors. Furthermore, we developed a novel predictive model for LN metastasis likelihood, designed to inform non-surgical treatment strategies, optimize personalized therapy plans, and potentially improve outcomes for patients who are ineligible for surgery.

Conclusions: This study offers a comprehensive analysis of the genetic and immune profiles in LUAD primary tumors with LN metastasis, identifying key immunogenomic patterns linked to metastatic progression. The predictive model derived from these insights marks a substantial advancement in personalized treatment, underscoring its potential to improve patient management.

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与肺腺癌淋巴结转移相关的空间免疫基因组模式

背景：伴有淋巴结（LN）转移的肺腺癌（LUAD）与不良预后有关，但其潜在机制在很大程度上仍未确定。本研究旨在阐明与LUAD淋巴结转移相关的免疫基因组图谱：我们对 257 例接受过手术治疗的 LUAD 患者队列采用了宽泛的下一代测序（NGS）技术，以描述原发肿瘤的分子图谱并识别可操作的驱动基因改变。此外，我们还在倾向得分匹配的队列中使用了多重免疫组化（mIHC）技术，这使我们能够详细描述原发性肿瘤的免疫微环境，同时保留细胞元簇、相互作用和邻近功能单元。通过整合来自 NGS 和 mIHC 的数据，我们成功确定了空间免疫基因组模式，并建立了 LN 转移的预测模型，该模型随后得到了独立验证：结果：我们的分析揭示了与LN转移阶段相关的独特免疫基因组学改变模式。具体来说，我们观察到 LN 转移原发肿瘤中 PIK3CG 和 ATM 等基因的突变频率增加。此外，LN 阳性原发肿瘤表现出更高的巨噬细胞和调节性 T 细胞元簇及其丰富的邻近单位（p 结论）：本研究对伴有LN转移的LUAD原发肿瘤的基因和免疫特征进行了全面分析，确定了与转移进展相关的关键免疫基因组模式。从这些洞察力中得出的预测模型标志着个性化治疗的重大进展，凸显了其改善患者管理的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Hematology & Oncology Medicine-Oncology

CiteScore

12.60

自引率

7.30%

发文量

审稿时长

6 weeks

期刊介绍： Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.