大细胞神经内分泌肺癌的治疗现状、生存及基因表达分析：一项中国的真实世界研究

Treatment status, survival and gene expression analysis of large-cell neuroendocrine lung carcinoma: a real-world study in China.

作者信息

Qi Fei, Zhang Minghang, Han Yi, Du Juan, Yang Hongjie, Zhang Hongmei, Zhang Yong, Zhang Tongmei

机构信息

General Department, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

Laboratory for Clinical Medicine, Capital Medical University, Beijing, China.

出版信息

Ther Adv Med Oncol. 2025 Apr 4;17:17588359251324900. doi: 10.1177/17588359251324900. eCollection 2025.

DOI:10.1177/17588359251324900

PMID:40290463

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12032454/

Abstract

BACKGROUND

Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare subtype of lung cancer that lacks standard treatment at present.

PURPOSE

This study aimed to investigate the treatment status, failure pattern, survival outcome, and gene expression profile of LCNEC in China.

DESIGN

This is a real-world retrospective study combined with transcriptome sequencing of LCNEC tumors.

METHODS

Patients with newly diagnosed LCNEC at Beijing Chest Hospital from 2015 to 2022 were retrospectively reviewed. Treatment, failure pattern, and survival were analyzed. Transcriptome sequencing of LCNEC and non-small-cell lung cancer was conducted for differentiated expressed genes exploration and enrichment analysis.

RESULTS

In all, 151 eligible patients met the criteria: stage I (24.5%), II (9.9%), IIIA (13.9%), and IIIB-IV (51.7%). Median progression-free survival (PFS) and overall survival (OS) were 7.9 and 17.8 months for an entire cohort of patients. For stage I/II and IIIA patients receiving radical operation or chemoradiation, 47 out of 77 cases developed treatment failure with 2-year cumulative systemic/distant failure (SF), locoregional failure (LRF), and overall failure rates of 65.2%, 52.7%, and 30.8%, respectively. Failure incidence increased with stage development. Stage III disease presented with a significantly higher cumulative SF rate (2-year, 57.3% vs 29.7%; = 0.010) but a similar LRF rate (2-year, 41.5% vs 37.6%, = 0.369) than stage I/II, achieving favorable SF-free survival and comparable LRF-free survival. Adding adjuvant chemotherapy to surgery reduced distant dissemination which translated into survival benefit (2-year SF, 53.7% vs 41.3%, = 0.055; 2-year OS, 37.1% vs 79.9%, < 0.001). For advanced LCNEC, immunochemotherapy and chemotherapy alone achieved PFS of 10.3 and 4.7 months, respectively ( = 0.045). Differential gene expression analysis revealed that antigen presentation/processing, chemokine signaling, CXCR4, and IFN-γ pathways were upregulated in LCNEC, suggesting the vulnerability of LCNEC to immunotherapy. Besides, , and may play vital roles in the LCNEC pathogenesis.

CONCLUSION

LCNEC is a highly aggressive disease and incorporation of immunotherapy might be an effective treatment option.

摘要

背景

大细胞神经内分泌肺癌（LCNEC）是一种罕见的肺癌亚型，目前缺乏标准治疗方案。

目的

本研究旨在调查中国LCNEC的治疗现状、失败模式、生存结果和基因表达谱。

设计

这是一项结合LCNEC肿瘤转录组测序的真实世界回顾性研究。

方法

回顾性分析2015年至2022年在北京胸科医院新诊断的LCNEC患者。分析治疗、失败模式和生存情况。对LCNEC和非小细胞肺癌进行转录组测序，以探索差异表达基因并进行富集分析。

结果

共有151例符合条件的患者：I期（24.5%）、II期（9.9%）、IIIA期（13.9%）和IIIB-IV期（51.7%）。整个队列患者的中位无进展生存期（PFS）和总生存期（OS）分别为7.9个月和17.8个月。对于接受根治性手术或放化疗的I/II期和IIIA期患者，77例中有47例出现治疗失败，2年累积全身/远处失败（SF）、局部区域失败（LRF）和总失败率分别为65.2%、52.7%和30.8%。失败发生率随分期进展而增加。III期疾病的累积SF率显著更高（2年，57.3%对29.7%；P = 0.010），但LRF率相似（2年，41.5%对37.6%，P = 0.369），与I/II期相比，实现了良好的无SF生存期和相当的无LRF生存期。手术加辅助化疗可减少远处转移，从而带来生存获益（2年SF，53.7%对41.3%，P = 0.055；2年OS，37.1%对79.9%，P < 0.001）。对于晚期LCNEC，免疫化疗和单纯化疗的PFS分别为10.3个月和4.7个月（P = 0.045）。差异基因表达分析显示，抗原呈递/加工、趋化因子信号传导、CXCR4和IFN-γ途径在LCNEC中上调，提示LCNEC对免疫治疗的易感性。此外，[此处原文可能缺失具体基因名称]可能在LCNEC发病机制中起重要作用。