AbstractBased on favorable outcomes and decreased propensity for lymph node and distant metastasis, multiple ground-glass nodules (GGNs) are now predominantly recognized as early-stage primary independent lung cancer. In this study, we discuss a case involving a patient with reoperative multifocal GGNs who was ultimately diagnosed with early multiple intrapulmonary metastases and multifocal primary lung cancers.

摘要基于良好的预后和降低淋巴结和远处转移的倾向，多发性磨玻璃结节（GGNs）现在主要被认为是早期原发性非依赖性肺癌。在这项研究中，我们讨论了一例涉及再次手术的多灶性GGN患者的病例，该患者最终被诊断出患有早期多发性肺内转移和多灶性原发性肺癌。

This patient exhibited multisite epidermal growth factor receptor (EGFR) mutations, including the classical L858R, exon 19 deletion and the rare V834L variant. Despite a high tumor burden and the presence of various EGFR driver mutations, the patient experienced prolonged dormancy and exceptionally slow lesion growth, even without any systemic treatment.

该患者表现出多位表皮生长因子受体（EGFR）突变，包括经典的L858R，外显子19缺失和罕见的V834L变体。尽管肿瘤负担很高，并且存在各种EGFR驱动突变，但即使没有任何全身治疗，患者也经历了长时间的休眠和异常缓慢的病变生长。

Our research indicates that the patient’s immune response against the tumor remained robust throughout the disease course. Furthermore, we found that pathways associated with integrin-mediated cell extracellular matrix adhesion played a role in activating her innate immune responses and regulating tumor dormancy.

我们的研究表明，患者对肿瘤的免疫反应在整个疾病过程中保持强劲。此外，我们发现与整合素介导的细胞-细胞外基质粘附相关的途径在激活她的先天免疫反应和调节肿瘤休眠中起作用。

Our findings suggest that the interplay between cancer cell mutations and the tumor microenvironment (TME) phenotype during tumor evolution contributed to this patient’s prolonged survival. Integrating these aspects for lung tumor stratification is expected to improve predictions of growth potential and aid in clinical decision making..

我们的发现表明，肿瘤进化过程中癌细胞突变与肿瘤微环境（TME）表型之间的相互作用有助于该患者的延长生存期。将这些方面整合到肺肿瘤分层中，有望改善对生长潜力的预测，并有助于临床决策。。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content, access via your institution

这是订阅内容的预览，可通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Subscribe to this journalReceive 6 digital issues and online access to articles111,21 € per yearonly 18,54 € per issueLearn moreBuy this articlePurchase on Springer LinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkout

订阅本期刊每年可收到6期数字期刊和在线访问文章111,21欧元每期仅18,54欧元了解更多在Springer Link上购买本文立即访问全文PDFBuy NOW价格可能需要缴纳结帐期间计算的当地税费

Additional access options:

其他访问选项：

Log in

登录

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

联系客户支持

Fig. 1: Pathological and radiologic images of the five tumors.Fig. 2: Mutational spectrum and phylogeny evolution analysis for five tumors in this patient.Fig. 3: Immune microenvironment analysis for the five tumors.Fig. 4: Pathway enrichment analysis of the four homologous tumors.

图1：五种肿瘤的病理和放射学图像。图2：该患者中五种肿瘤的突变谱和系统发育进化分析。图3：五种肿瘤的免疫微环境分析。图4：四种同源肿瘤的途径富集分析。

ReferencesMazzone PJ, Lam L. Evaluating the patient with a pulmonary nodule: a review. JAMA. 2022;327:264–73.Article

参考文献Mazzone PJ，Lam L.评估肺结节患者：综述。杰玛。2022年；327:264–73.文章

PubMed

PubMed

Google Scholar

谷歌学者

Detterbeck FC, Marom EM, Arenberg DA, Franklin WA, Nicholson AG, Travis WD, et al. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification.

Detterbeck FC，Marom EM，Arenberg DA，Franklin WA，Nicholson AG，Travis WD等。IASLC肺癌分期项目：将TNM分期规则应用于肺癌的背景数据和建议，表现为多个结节，具有磨玻璃或鳞状特征或即将出版的第八版TNM分类中涉及的肺炎类型。

J Thorac Oncol. 2016;11:666–80.Article .

J Thorac肿瘤。2016年；11:666-80.文章。

PubMed

PubMed

Google Scholar

谷歌学者

Gorospe L, Gómez-Bermejo MÁ, Paredes-Rodríguez P, Mirambeaux-Villalona RM, Fra-Fernández S, Muñoz-Molina GM, et al. Three synchronous lung cancers in the same lung segment: triple trouble? Arch Bronconeumol. 2023;59:458–60.Article

Gorospe L，Gómez Bermejo MÁ，Paredes Rodríguez P，Mirambeaux Villalona RM，Fra Fernández S，Muñoz Molina GM等。同一肺段的三种同步肺癌：三重麻烦？弓形支气管。2023年；59:458–60.文章

PubMed

PubMed

Google Scholar

谷歌学者

Li R, Li X, Xue R, Yang F, Wang S, Li Y, et al. Early metastasis detected in patients with multifocal pulmonary ground-glass opacities (GGOs). Thorax. 2018;73:290–2.Article

Li R，Li X，Xue R，Yang F，Wang S，Li Y，et al。多灶性肺毛玻璃样混浊（GGO）患者早期转移的检测。胸部。2018年；73:290–2.文章

PubMed

PubMed

Google Scholar

谷歌学者

Nakamura S, Fukui T, Taniguchi T, Usami N, Kawaguchi K, Ishiguro F, et al. Prognostic impact of tumor size eliminating the ground glass opacity component: modified clinical T descriptors of the tumor, node, metastasis classification of lung cancer. J Thorac Oncol. 2013;8:1551–7.Article .

Nakamura S，Fukui T，Taniguchi T，Usami N，Kawaguchi K，Ishiguro F等。消除磨玻璃不透明度成分的肿瘤大小对预后的影响：肺癌肿瘤，淋巴结，转移分类的改进临床T描述符。J胸部肿瘤学。2013年；8： 1551年至1557年。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Mansouri S, Heylmann D, Stiewe T, Kracht M, Savai R. Cancer genome and tumor microenvironment: Reciprocal crosstalk shapes lung cancer plasticity. Elife. 2022;11:e79895.Article

Mansouri S，Heylmann D，Stiewe T，Kracht M，Savai R.癌症基因组和肿瘤微环境：相互串扰影响肺癌的可塑性。埃利夫。2022年；11： e79895。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rodrigues FS, Ciccarelli FD, Malanchi I. Reflected stemness as a potential driver of the tumour microenvironment. Trends Cell Biol. 2022;32:979–87.Article

Rodrigues FS，Ciccarelli FD，Malanchi I.反映了干性作为肿瘤微环境的潜在驱动因素。趋势细胞生物学。2022年；32:979–87.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chae YK, Viveiros P, Lopes G, Sukhadia B, Sheikh MM, Saravia D, et al. Clinical and immunological implications of frameshift mutations in lung cancer. J Thorac Oncol. 2019;14:1807–17.Article

Chae YK，Viveiros P，Lopes G，Sukhadia B，Sheikh MM，Saravia D等。肺癌移码突变的临床和免疫学意义。J胸部肿瘤学。2019年；14： 1807-17.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Dejima H, Hu X, Chen R, Zhang J, Fujimoto J, Parra ER, et al. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features. Nat Commun. 2021;12:2722.Article

。纳特公社。2021年；12： 2722条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wu C, Zhao C, Yang Y, He Y, Hou L, Li X, et al. High discrepancy of driver mutations in patients with NSCLC and ansynchronous multiple lung ground-glass nodules. J Thorac Oncol. 2015;10:778–83.Article

Wu C，Zhao C，Yang Y，He Y，Hou L，Li X，et al。NSCLC和非同步多发性肺磨玻璃结节患者驱动突变的高度差异。J胸部肿瘤学。2015年；10： 778-83.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kobayashi Y, Mitsudomi T, Sakao Y, Yatabe Y. Genetic features of pulmonary adenocarcinoma presenting with ground-glass nodules: the differences between nodules with and without growth. Ann Oncol. 2015;26:156–61.Article

。安·昂科尔。2015年；26:156–61.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen N, Fang W, Zhan J, Hong S, Tang Y, Kang S, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-Driven NSCLC: Implication for optional immune targeted therapy for NSCLC patients with EGFR mutation. J Thorac Oncol. 2015;10:910–23.Article

Chen N，Fang W，Zhan J，Hong S，Tang Y，Kang S等。通过EGFR激活上调PD-L1介导EGFR驱动的NSCLC中的免疫逃逸：对EGFR突变的NSCLC患者进行选择性免疫靶向治疗的意义。J胸部肿瘤学。2015年；10： 910–23.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.Article

施赖伯路，老LJ，史密斯MJ。癌症免疫编辑：整合免疫在癌症抑制和促进中的作用。科学。2011年；331:1565–70.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mino-Kenudson M, Schalper K, Cooper W, Dacic S, Hirsch FR, Jain D, et al. Predictive biomarkers for immunotherapy in lung cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee. J Thorac Oncol. 2022;17:1335–54.Article

Mino Kenudson M，Schalper K，Cooper W，Dacic S，Hirsch FR，Jain D等。肺癌免疫治疗的预测性生物标志物：国际肺癌病理学研究协会委员会的观点。J胸部肿瘤学。2022年；17： 1335-54.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zou XL, Li XB, Ke H, Zhang GY, Tang Q, Yuan J, et al. Prognostic value of neoantigen load in immune checkpoint inhibitor therapy for cancer. Front Immunol. 2021;12:689076.Article

邹XL，李晓斌，柯浩，张GY，唐Q，袁杰，等。新抗原负荷在免疫检查点抑制剂治疗癌症中的预后价值。前免疫。2021年；12： 689076条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kai F, Drain AP, Weaver VM. The extracellular matrix modulates the metastatic journey. Dev Cell. 2019;49:332–46.Article

Kai F，Drain AP，Weaver VM。细胞外基质调节转移过程。开发单元。2019年；49:332-46.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barkan D, Green JE, Chambers AF. Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur J Cancer. 2010;46:1181–8.Article

Barkan D，Green JE，Chambers AF.细胞外基质：从休眠过渡到转移性生长的看门人。Eur J癌症。2010年；46:1181-8.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barkan D, Chambers AF. β1-Integrin: A potential therapeutic target in the battle against cancer recurrence. Clin Cancer Res. 2011;17:7219–23.Article

。Clin Cancer Res.2011；17： 7219–23.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kadota K, Nitadori JI, Sima CS, Ujiie H, Rizk NP, Jones DR, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small Stage I lung adenocarcinomas. J Thorac Oncol. 2015;10:806–14.Article .

Kadota K，Nitadori JI，Sima CS，Ujiie H，Rizk NP，Jones DR等。肿瘤通过空气空间扩散是一种重要的侵袭模式，并影响小I期肺腺癌有限切除后复发的频率和位置。J胸部肿瘤学。2015年；10： 806-14条。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesFundingFundingThis work was supported by program for Youth Innovation in Future Medicine of CQMU (No. W0172), Postdoctoral Science Foundation of China (No. 2022T150777) and Postdoctoral Science Foundation of Chongqing (No. 2021XM1028) to Yuan Peng.Author informationAuthor notesThese authors contributed equally: Yuan Peng, Chuan Zeng.Authors and AffiliationsDepartment of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, ChinaYuan Peng, Chuan Zeng, Rongxin Liao, Yan Zhou & Zhenzhou YangGuchengtai Community Health Center of Chengxi District, Xining, 810000, ChinaYuan PengGeneplus-Beijing, Beijing, 102206, ChinaLu ShenAuthorsYuan PengView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了重庆医科大学未来医学青年创新计划（编号W0172），中国博士后科学基金（编号2022T150777）和重庆博士后科学基金（编号2021XM1028）的袁鹏的支持。作者信息作者注意到这些作者做出了同样的贡献：袁鹏，曾川。作者和所属机构重庆医科大学附属第二医院肿瘤中心，重庆，400010，彭华远，曾川，廖荣新，兖州和郑州市城西区杨古城台社区卫生中心，西宁，810000，彭华远北京，102206，中国路作者袁鹏维作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarChuan ZengView author publicationsYou can also search for this author in

PubMed Google ScholarChuan ZengView作者出版物您也可以在

PubMed Google ScholarRongxin LiaoView author publicationsYou can also search for this author in

PubMed Google ScholarRongxin LiaoView作者出版物您也可以在

PubMed Google ScholarLu ShenView author publicationsYou can also search for this author in

PubMed Google ScholarLu ShenView作者出版物您也可以在

PubMed Google ScholarYan ZhouView author publicationsYou can also search for this author in

PubMed Google ScholarYan ZhouView作者出版物您也可以在

PubMed Google ScholarZhenzhou YangView author publicationsYou can also search for this author in

PubMed谷歌学者Zhenzhou YangView作者出版物您也可以在

PubMed Google ScholarContributionsYuan Peng and Chuan Zeng designed the study, analysed data, interpreted data, and wrote the report. Rongxin Liao collected the clinical data and provided the pathology results. Lu Shen prepared the figure. Chuan Zeng contributed to clinical care of the patient.

PubMed谷歌学术贡献Yuan Peng和Chuan Zeng设计了这项研究，分析了数据，解释了数据，并撰写了报告。廖荣新收集了临床资料并提供了病理结果。陆深准备了这个数字。曾川为患者的临床护理做出了贡献。

Zhenzhou Yang and Yan Zhou designed the study, did the critical review and finalised the report. Written informed consent to publication was obtained.Corresponding authorsCorrespondence to.

杨振洲和严洲设计了这项研究，进行了批判性审查并完成了报告。获得了出版的书面知情同意书。通讯作者通讯。

Yan Zhou or Zhenzhou Yang.Ethics declarations

Yan Zhou或Zhenzhou Yang。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethics approval

道德认可

Personal and clinical data were approved by the Ethics Committees of the Second Affiliated Hospital of Chongqing Medical University and the approval number was (2022)285.

个人和临床数据经重庆医科大学第二附属医院伦理委员会批准，批准号为（2022）285。

Consent to participate

同意参与

Informed consent was obtained from the patient.

获得患者的知情同意。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articlePeng, Y., Zeng, C., Liao, R.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。权利和许可Pringer Nature或其许可人（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Peng，Y.，Zeng，C.，Liao，R。

et al. Innate immune dynamics in the context of multisite EGFR mutations in lung adenocarcinoma..

肺腺癌中多位点EGFR突变背景下的先天免疫动力学。。

Genes Immun (2024). https://doi.org/10.1038/s41435-024-00288-1Download citationReceived: 08 November 2023Revised: 12 July 2024Accepted: 18 July 2024Published: 06 August 2024DOI: https://doi.org/10.1038/s41435-024-00288-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

基因免疫（2024）。https://doi.org/10.1038/s41435-024-00288-1Download引文接收日期：2023年11月8日修订日期：2024年7月12日接受日期：2024年7月18日发布日期：2024年8月6日OI：https://doi.org/10.1038/s41435-024-00288-1Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供