Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.102.36

Haoran Li, Yuanyuan Wang, Yang Wang, Huihui He, Junya Li, Yanning Su, Fanrui Kong, Xiangli Liu, Liuhui Cheng, Ya Li

Background: The discrimination between benign and malignant pulmonary space-occupying lesions and the classification of pathological subtypes of lung cancer are critical for clinical decision-making. However, conventional methods often suffer from insufficient utilization of multi-source clinical data and poor interpretability of deep learning models. This study investigates the performance of interpretable deep learning algorithms in diagnosing benign versus malignant pulmonary space-occupying lesions and classifying pathological subtypes of lung cancer, using a hybrid architecture based on Tab-Transformer-designed for tabular data and Residual Multi-Layer Perceptron (ResMLP), referred to as TT-ResMLP.Methods: Data including radiological characteristics, medical history, and laboratory findings from 345 patients with pathologically confirmed pulmonary space-occupying lesions were collected. The dataset was randomly split into a development set and a test set at an 8:2 ratio. Stable features were selected using the Spearman correlation test and the Least Absolute Shrinkage and Selection Operator (LASSO). The Synthetic Minority Over-sampling Technique (SMOTE) was employed to balance the samples, and 10-fold cross-validation was used to enhance model generalizability. Models were constructed using the Tab-Transformer algorithm, the ResMLP algorithm, and the TT-ResMLP hybrid. Model performance was evaluated using receiver operating characteristic (ROC) curves, the area under the curve (AUC), accuracy, specificity, sensitivity, and micro-averaged ROC (micro-ROC). SHapley Additive exPlanations (SHAP) analysis was performed based on the optimal model.Results: In the benign vs malignant diagnosis task, all three models performed well. The Tab-Transformer model demonstrated the best performance on the test set, followed by TT-ResMLP and ResMLP. SHAP analysis of the top-performing Tab-Transformer model revealed that the feature importance ranking was: age, pleural indentation, thrombin time, mean density, and ground-glass opacity. Pleural indentation contributed substantially to malignant diagnosis, and its contribution was further enhanced with increasing age and decreasing thrombin time. In the lung cancer subtype classification task, all three models exhibited excellent performance, with the TT-ResMLP hybrid showing the best overall performance. SHAP analysis further revealed that the Lung Imaging Reporting and Data System (Lung-RADS) category held high importance across all three pathological subtypes. Male gender was positively associated with the prediction of squamous cell carcinoma. Neuron-specific enolase (NSE) played a significant role in predicting small cell carcinoma. For adenocarcinoma, the diagnostic probability was positively correlated with the Lung-RADS category, a relationship more pronounced at lower prothrombin time (PT) values. In contrast, a negative correlation was

背景：肺占位性病变良恶性的鉴别及肺癌病理亚型的分型对临床决策至关重要。然而，传统的方法往往存在对多源临床数据利用不足和深度学习模型可解释性差的问题。本研究研究了可解释深度学习算法在诊断良性与恶性肺占位性病变和分类肺癌病理亚型方面的性能，使用基于为表格数据设计的标签转换器和残余多层感知器（ResMLP）的混合架构，称为TT-ResMLP。方法：收集345例经病理证实的肺部占位性病变患者的影像学特征、病史及实验室检查结果。数据集以8:2的比例随机分为开发集和测试集。使用Spearman相关检验和最小绝对收缩和选择算子（LASSO）选择稳定特征。采用合成少数派过采样技术（SMOTE）来平衡样本，并采用10倍交叉验证来增强模型的可泛化性。使用Tab-Transformer算法、ResMLP算法和TT-ResMLP混合算法构建模型。采用受试者工作特征（ROC）曲线、曲线下面积（AUC）、准确性、特异性、敏感性和微平均ROC （micro-ROC）来评价模型的性能。基于最优模型进行SHapley加性解释（SHAP）分析。结果：在良恶性诊断任务中，三种模型均表现良好。Tab-Transformer模型在测试集中表现最佳，其次是TT-ResMLP和ResMLP。对表现最好的Tab-Transformer模型进行SHAP分析显示，特征重要性排序为：年龄、胸膜压痕、凝血酶时间、平均密度和毛玻璃不透明度。胸膜压痕对恶性诊断的贡献很大，随着年龄的增加和凝血酶时间的缩短，其贡献进一步增强。在肺癌亚型分类任务中，三种模型均表现优异，其中TT-ResMLP杂交模型综合表现最佳。SHAP分析进一步显示，肺成像报告和数据系统（Lung- rads）类别在所有三种病理亚型中都具有很高的重要性。男性与鳞状细胞癌的预测呈正相关。神经元特异性烯醇化酶（NSE）在预测小细胞癌中发挥重要作用。对于腺癌，诊断概率与Lung-RADS分类呈正相关，这种关系在凝血酶原时间（PT）较低时更为明显。相比之下，在鳞状细胞癌和小细胞癌亚组中观察到负相关，尽管性别和NSE水平可以增强其促成风险的预测。特征决策边界分析表明，Lung-RADS分级对腺癌的鉴别能力较强，而NSE对小细胞癌的鉴别能力较强。结论：TT-ResMLP混合结构对肺占位性病变的良恶性诊断及肺癌病理亚型分类具有较好的应用价值。该模型具有良好的可解释性，有助于识别关键预测特征并揭示其相互作用机制，从而为更深入地了解肺癌生物学和临床决策支持提供有效工具。

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引用次数: 0

[Research Progress on Interleukin-6 in Screening and Prognosis of Patients  with Non-small Cell Lung Cancer]. [白细胞介素-6在 非小细胞肺癌筛查及预后中的研究进展]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.101.18

Dongyang Xu, Chenxiao Qiao, Xiaoying Zhang, Qingchao Kong, Xiang Ji

Non-small cell lung cancer (NSCLC), the predominant histological subtype of lung cancer, mandates precise screening and accurate prognostic assessment to guide therapeutic strategies and improve patient survival. The initiation and progression of NSCLC are intimately linked to inflammatory responses. Interleukin-6 (IL-6), a pivotal inflammatory mediator, critically modulates the tumor microenvironment, immune evasion, tumor progression, and therapy resistance in NSCLC. Recent evidence indicates that IL-6 not only participates in the biological behavior of NSCLC but also holds promise as a potential biomarker for early detection and prognostication. This review summarizes the role of IL-6 in NSCLC screening, treatment-related adverse events, and its utility in the management of NSCLC-associated comorbidities. .

非小细胞肺癌（NSCLC）是肺癌的主要组织学亚型，需要精确的筛查和准确的预后评估来指导治疗策略和提高患者生存率。非小细胞肺癌的发生和发展与炎症反应密切相关。白细胞介素-6 （IL-6）是一种关键的炎症介质，在非小细胞肺癌中对肿瘤微环境、免疫逃避、肿瘤进展和治疗抵抗起到关键调节作用。最近的证据表明，IL-6不仅参与非小细胞肺癌的生物学行为，而且有望作为早期发现和预后的潜在生物标志物。本文综述了IL-6在非小细胞肺癌筛查、治疗相关不良事件及其在非小细胞肺癌相关合并症管理中的作用。 。

引用次数: 0

[Expert Consensus on the Clinical Application of Sodium Cantharidinate and Vitamin B6 Injection]. [斑蝥素酸钠维生素B6注射液临床应用专家共识]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.102.37

Cancer prevention and control in China face severe challenges. Although targeted therapy and immunotherapy have made remarkable progress, chemotherapy remains a cornerstone of comprehensive cancer treatment, and its toxic side effects pose a significant challenge in clinical practice. As a compound formulation exhibiting both antitumor and toxicity-reducing effects, Sodium cantharidinate and vitamin B6 injection has been utilized in clinical practice in China for over two decades. However, standardized guidelines for its application remain lacking in routine clinical use. To address this gap, the Lung Cancer Specialty Committee of Chinese Elderly Health Care Association organized a panel of experts to develop this consensus document, drawing on current evidence-based data and accumulated clinical experience. This consensus provides a systematic elaboration of the preparation's pharmacological mechanisms and pharmacokinetic profiles, and offers specific recommendations for its clinical application across various malignancies, including lung cancer and hepatocellular carcinoma. The primary objective of this consensus is to establish standardized guidance for clinicians regarding the appropriate use of Sodium cantharidinate and vitamin B6 injection, thereby promoting its rational application and ultimately enhancing treatment efficacy and quality of life for cancer patients. .

中国癌症防治面临严峻挑战。虽然靶向治疗和免疫治疗取得了显著进展，但化疗仍然是癌症综合治疗的基石，其毒副作用给临床实践带来了重大挑战。斑蝥素酸钠维生素B6注射液作为一种具有抗肿瘤和降毒双重作用的复方制剂，在中国临床应用已有二十多年的历史。然而，在常规临床应用中，仍缺乏标准化的应用指南。为了解决这一差距，中国老年保健协会肺癌专业委员会组织了一个专家小组，根据目前的循证数据和积累的临床经验，制定了这一共识文件。这一共识提供了该制剂的药理学机制和药代动力学特征的系统阐述，并为其在各种恶性肿瘤（包括肺癌和肝细胞癌）中的临床应用提供了具体建议。本共识的主要目的是为临床医生建立规范的斑蝥素酸钠和维生素B6注射液的合理使用指导，从而促进其合理应用，最终提高癌症患者的治疗效果和生活质量。

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引用次数: 0

[Integrative Analysis of Multi-source Public Databases to Screen Core Genes  for Constructing A Prognostic Risk Model in Lung Adenocarcinoma]. [综合分析多源公共数据库筛选核心基因 构建肺腺癌预后风险模型]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.102.38

Chengmeng Wang, Lu Zhang, Yu Zhang, Yu Wang, Meng Wang

Background: Tyrosine kinase inhibitors (TKIs) resistance poses a significant challenge in the targeted therapy of lung adenocarcinoma (LUAD), highlighting the need to identify key molecular markers associated with both drug resistance and prognosis to guide precision treatment. This study aimed to elucidate the molecular mechanisms underlying TKIs resistance in LUAD, identify core differentially expressed genes (DEGs), clarify the relationships between different gene clusters and patient survival/drug response, and construct and validate a prognostic risk model for LUAD, thereby providing a foundation for precision therapy and prognostic assessment.Methods: Multiple LUAD-related datasets, including GSE162045 and GSE114647, were integrated. Core overlapping DEGs were identified using Venn diagrams, and a gene correlation network was constructed. Consensus clustering was applied for sample grouping, combined with t-SNE dimensionality reduction to visually validate clustering stability and distinctness. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to explore the functional enrichment of DEGs. The 50% maximal inhibitory concentration (IC50) values of 12 drugs were compared across clusters to evaluate differences in drug sensitivity. Prognosis-related core genes were selected via LASSO regression to construct a risk model, whose performance was subsequently validated in the GSE31210 cohort using Sankey diagrams, Kaplan-Meier survival curves, and receiver operating characteristic (ROC) curves. Expression differences of core genes among clusters and between risk groups were analyzed, and Kaplan-Meier curves were plotted to assess the association between individual gene expression and survival. The expression of PLEK2 in LUAD tissues was analyzed based on multiple datasets (GSE19804, GSE19188, GSE44077, GSE30219), and its protein level in epidermal growth factor receptor (EGFR)-TKIs-resistant LUAD cell lines was detected by Western blot.Results: Twelve core DEGs (e.g., HMGA1, PLEK2) were identified. When the cluster number (K) was set to 2, samples were stably divided into Cluster A and Cluster B. The expression of 10 core genes was significantly different between the two clusters (P<0.0001), and the patients in Cluster A exhibited significantly better overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) compared to those in Cluster B. Notable differences were observed in the mutation profiles of high-frequency genes such as TP53, KRAS and EGFR between the clusters. KEGG enrichment analysis revealed that the DEGs were primarily enriched in pathways such as "Cell cycle" and "Neuroactive ligand-receptor interaction". GSEA indicated significant associations with gene sets related to the malignant progression of tumors. Drug sensitivity analysis demonstrated significant differences in IC50 values for

背景：酪氨酸激酶抑制剂（Tyrosine kinase inhibitors, TKIs）耐药是肺腺癌（LUAD）靶向治疗的一个重大挑战，强调需要识别与耐药和预后相关的关键分子标志物，以指导精准治疗。本研究旨在阐明LUAD中TKIs耐药的分子机制，鉴定核心差异表达基因（DEGs），明确不同基因簇与患者生存/药物反应的关系，构建并验证LUAD预后风险模型，为精准治疗和预后评估提供基础。方法：整合多个luad相关数据集，包括GSE162045和GSE114647。利用维恩图识别核心重叠基因，构建基因相关网络。采用共识聚类对样本进行分组，并结合t-SNE降维直观验证聚类的稳定性和独特性。通过京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）来探索deg的功能富集。比较12种药物的50%最大抑制浓度（IC50）值，以评估药物敏感性的差异。通过LASSO回归选择与预后相关的核心基因构建风险模型，随后在GSE31210队列中使用Sankey图、Kaplan-Meier生存曲线和受试者工作特征（ROC）曲线对其性能进行验证。分析核心基因在集群间和风险组间的表达差异，绘制Kaplan-Meier曲线，评估个体基因表达与生存之间的关系。基于多个数据集（GSE19804、GSE19188、GSE44077、GSE30219）分析PLEK2在LUAD组织中的表达，并通过Western blot检测其在表皮生长因子受体(EGFR)- tkis耐药LUAD细胞株中的表达水平。结果：鉴定出12个核心DEGs（如HMGA1， PLEK2）。当聚类数(K)设为2时，将样本稳定分为A类和b类，两类间10个核心基因的表达量存在显著差异(p)。结论：本研究构建的风险模型能够有效预测LUAD患者的预后。PLEK2在LUAD中高表达，并与EGFR-TKIs耐药性相关，这表明PLEK2有可能作为预后生物标志物和治疗靶点。

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引用次数: 0

[Research Advances on the Autophagy and Ferroptosis  in the Development and Treatment of Lung Cancer]. [自噬和铁下垂 在肺癌发生与治疗中的研究进展]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.102.41

Chengqi Jiang, Xueping Cui, Li Zheng, Chengkun Deng, Ruoshan Huang, Bo Hou, Junfeng Wang

Lung cancer remains a life-threatening malignancy with complex pathogenesis. This paper provides a systematic review of autophagy and ferroptosis-related signaling pathways, key regulatory factors, and their associated mechanisms, including the nuclear receptor coactivator 4 (NCOA4)-mediated ferritin autophagy-ferroptosis axis, mitochondrial autophagy, lipid droplet autophagy, circadian autophagy, chaperone-mediated autophagy, etc.. The review elucidates the roles of the tumor microenvironment and non-coding RNAs in autophagy-ferroptosis processes in lung cancer. Furthermore, it explores the potential of modern drugs and active components from traditional Chinese medicine to improve lung cancer outcomes by targeting autophagy and ferroptosis, proposing that targeting their interactive pathways could offer novel therapeutic strategies for lung cancer. .

肺癌是一种发病机制复杂、危及生命的恶性肿瘤。本文系统综述了自噬和凋亡相关的信号通路、关键调控因子及其相关机制，包括核受体共激活因子4 （NCOA4）介导的铁蛋白自噬-凋亡轴、线粒体自噬、脂滴自噬、昼夜节律自噬、伴侣介导的自噬等。本文综述了肿瘤微环境和非编码rna在肺癌自噬-铁凋亡过程中的作用。此外，该研究还探索了现代药物和中药活性成分通过靶向自噬和铁下垂改善肺癌预后的潜力，提出靶向它们的相互作用途径可能为肺癌提供新的治疗策略。 。

引用次数: 0

[Research Progress of TNMB Staging in Lung Cancer]. [肺癌TNMB分期研究进展]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.106.28

Yuanyuan Zhan, Yue Li, Cheng Shen

Lung cancer is the malignant tumor with the highest incidence and mortality in China, and accurate clinical staging is crucial for judging its prognosis and formulating treatment strategies. Currently, the internationally recognized tumor-nodule-metastasis (TNM) staging system centers on tumor anatomical characteristics but struggles to reflect the biological essence of tumors. Based on the TNM staging, the TNM-blood (TNMB) staging incorporates blood molecular biomarkers to achieve multi-dimensional assessment of anatomical and biological characteristics. Initially applied to cutaneous T-cell lymphoma, it has gradually expanded to the field of lung cancer in recent years. This review summarizes the existing research and applications of TNMB staging in lung cancer, comparatively analyzes the differences between TNMB and the traditional TNM staging in terms of staging basis, evaluation dimensions and clinical efficacy, and further summarizes the existing types of molecular biomarkers related to B staging as well as those expected to be included in B staging. .

肺癌是中国发病率和死亡率最高的恶性肿瘤，准确的临床分期对于判断其预后和制定治疗策略至关重要。目前，国际上公认的肿瘤-结节-转移（TNM）分期体系以肿瘤解剖特征为中心，难以反映肿瘤的生物学本质。在TNM分期的基础上，TNM-blood （TNMB）分期纳入血液分子生物标志物，实现对解剖学和生物学特征的多维评估。最初应用于皮肤t细胞淋巴瘤，近年来逐渐扩展到肺癌领域。本文综述了TNMB分期在肺癌中的现有研究与应用，对比分析了TNMB与传统TNM分期在分期依据、评价维度、临床疗效等方面的差异，并进一步总结了现有与B分期相关的分子生物标志物类型以及有望纳入B分期的分子生物标志物类型。

引用次数: 0

[Progress in Immunotherapy for Pulmonary Lymphoepithelioma Carcinoma]. 肺淋巴上皮瘤的免疫治疗进展

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.101.17

Weizhen Sun, Yuheng Zhou, Shoucheng Feng, Yaobin Lin, Nengqi Lin, Hao Long

Pulmonary lymphoepithelioma carcinoma (PLEC), a rare non-small cell lung cancer subtype strongly associated with Epstein-Barr virus (EBV) infection, currently lacks a standardized treatment regimen. Conventional platinum-based systemic chemoradiotherapy remains the primary approach. In recent years, its distinctive pathological features and tumor immune microenvironment have established a compelling rationale for immune checkpoint inhibitors (ICIs). Clinical studies have demonstrated promising efficacy and acceptable safety of ICIs, both as monotherapy and in combination with chemotherapy, in patients with advanced and resectable PLEC. Neoadjuvant immunotherapy has also emerged as a viable strategy to downstage tumors and improve resectability in operable cases. However, the rarity of PLEC has limited the availability of large-scale prospective trials, and current evidence is predominantly derived from retrospective analyses. Key challenges, including predictive biomarkers, mechanisms of immunotherapy, and optimal combination strategies, remain to be addressed. This review systematically summarizes the current clinical evidence, molecular mechanisms, and immune microenvironment characteristics of PLEC, and discusses future research directions. .

肺淋巴上皮癌（PLEC）是一种罕见的非小细胞肺癌亚型，与eb病毒（EBV）感染密切相关，目前缺乏标准化的治疗方案。传统的以铂为基础的全身放化疗仍然是主要的方法。近年来，其独特的病理特征和肿瘤免疫微环境为免疫检查点抑制剂（ici）的应用建立了令人信服的理论基础。临床研究已经证明，对于晚期可切除PLEC患者，无论是单独治疗还是联合化疗，ICIs都具有良好的疗效和可接受的安全性。新辅助免疫治疗也已成为降低肿瘤分期和提高可手术病例可切除性的可行策略。然而，PLEC的罕见性限制了大规模前瞻性试验的可用性，目前的证据主要来自回顾性分析。关键的挑战，包括预测性生物标志物、免疫治疗机制和最佳联合策略，仍有待解决。本文系统总结了目前PLEC的临床证据、分子机制、免疫微环境特征，并对未来的研究方向进行了探讨。 。

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引用次数: 0

[Molecular Mechanism of Neutrophils Driving the Progression of Lung Adenocarcinoma]. 中性粒细胞驱动肺腺癌进展的分子机制。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-10-20 DOI: 10.3779/j.issn.1009-3419.2025.106.29

Xiaoya Li, Long Li

Lung cancer is one of the most prevalent and lethal malignant tumors worldwide, with lung adenocarcinoma (LUAD) being a major subtype. In recent years, research has revealed that the tumor microenvironment (TME) plays a crucial role in the development and progression of LUAD. Notably, the role of neutrophils has increasingly garnered attention. Studies have shown that neutrophils can differentiate into various phenotypes within the TME, exhibiting multiple pro-tumorigenic functions. Additionally, neutrophils can secrete neutrophil extracellular traps (NETs) in response to certain stimuli. Although NETs possess anti-tumor characteristics, an increasing number of studies have uncovered their multifaceted pro-tumor functions. This review describes the role of neutrophils in the initiation, development, and metastasis of LUAD, focusing on immunoregulation, cellular metabolism, genetics, and various molecular mechanisms. .

肺癌是世界范围内最常见和最致命的恶性肿瘤之一，肺腺癌（LUAD）是一个主要亚型。近年来的研究表明，肿瘤微环境（tumor microenvironment， TME）在LUAD的发生发展中起着至关重要的作用。值得注意的是，中性粒细胞的作用越来越受到关注。研究表明，中性粒细胞可以在TME内分化成各种表型，表现出多种促肿瘤功能。此外，中性粒细胞可以分泌中性粒细胞胞外陷阱（NETs）响应某些刺激。虽然net具有抗肿瘤的特性，但越来越多的研究发现其具有多方面的促肿瘤功能。本文综述了中性粒细胞在LUAD的发生、发展和转移中的作用，重点介绍了免疫调节、细胞代谢、遗传学和各种分子机制。 。

引用次数: 0

[Role and Mechanism of Hyaluronic Acid-modified Milk Exosomes  in Reversing Pemetrexed Resistance in Lung Adenocarcinoma Cells]. [透明质酸修饰乳外泌体 在逆转肺腺癌细胞培美曲塞耐药中的作用及机制]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-09-20 DOI: 10.3779/j.issn.1009-3419.2025.102.35

Lan Wu, Jie Lei, Hui Li

Background: Lung cancer currently ranks first globally in both incidence and mortality. Pemetrexed (PMX) serves as a first-line treatment for lung adenocarcinoma (LUAD), but the patients often develop drug resistance during therapy. Milk exosome (mEXO) have the advantages of low immunogenicity, high tissue affinity, and low cost, and mEXO itself has anti-tumor effects. Hyaluronan (HA) naturally bind to CD44, a receptor which is highly expressed in LUAD tissues. This study aims to construct hyaluronan-modified milk exosome (HA-mEXO) and preliminarily investigate their molecular mechanisms for reversing PMX resistance through cellular experiments.

Methods: Exosomes were extracted from milk using high-speed centrifugation, and HA-mEXO was constructed. PMX-resistant A549 and PC-9 cell lines were treated with mEXO and HA-mEXO, respectively. CCK-8 assays, colony formation assays, Transwell assays, and flow cytometry were performed to evaluate proliferation, colony formation, migration, invasion, and apoptosis phenotypes in the treated resistant cell lines. Finally, transcriptomic sequencing, analysis, and cellular functional recovery experiments were conducted to investigate the mechanism by which HA-mEXO reverses PMX resistance in LUAD cells.

Results: The expression of CD44 in A549 and PC-9 LUAD drug-resistant cell lines was significantly higher than that in parental cells, and the uptake rate of HA-mEXO by drug-resistant cell lines was significantly higher than that of mEXO. Compared to the mEXO group, HA-mEXO-treated A549 and PC-9 resistant cells exhibited significantly reduced half maximal inhibitory concentration (IC50) values for PMX, markedly diminished clonogenic, migratory, and invasive capabilities, and a significantly increased proportion of apoptotic cells. Western blot analysis revealed that, compared to parental cells, A549 and PC-9 drug-resistant cells exhibited downregulated ZNF516 expression and upregulated ABCC5 expression. Immunofluorescence analysis revealed that HA-mEXO treatment downregulated ABCC5 expression in A549 and PC-9 drug-resistant cells compared to the PBS group, whereas co-treatment with HA-mEXO and ZNF516 knockdown showed no significant change in ABCC5 expression.

Conclusions: HA-mEXO carrying ZNF516 suppress ABCC5 expression, thereby enhancing the sensitivity of A549 and PC-9 LAUD drug-resistant cells to PMX.

背景：目前肺癌的发病率和死亡率均居全球首位。培美曲塞（Pemetrexed， PMX）作为肺腺癌（LUAD）的一线治疗药物，但患者在治疗过程中经常出现耐药性。牛奶外泌体（Milk exosome, mEXO）具有免疫原性低、组织亲和力高、成本低等优点，而且mEXO本身具有抗肿瘤作用。透明质酸（HA）自然结合CD44，一个在LUAD组织中高度表达的受体。本研究旨在构建透明质酸修饰乳外泌体（HA-mEXO），并通过细胞实验初步探讨其逆转PMX耐药的分子机制。方法：采用高速离心法从牛奶中提取外泌体，构建HA-mEXO。分别用mEXO和HA-mEXO处理耐pmx的A549和PC-9细胞系。CCK-8测定、菌落形成测定、Transwell测定和流式细胞术评估处理后耐药细胞系的增殖、菌落形成、迁移、侵袭和凋亡表型。最后，通过转录组测序、分析和细胞功能恢复实验来研究HA-mEXO在LUAD细胞中逆转PMX耐药性的机制。结果：CD44在A549和PC-9 LUAD耐药细胞株中的表达明显高于亲本细胞，耐药细胞株对HA-mEXO的摄取率明显高于对mEXO的摄取。与mEXO组相比，ha -mEXO处理的A549和PC-9耐药细胞对PMX的最大抑制浓度（IC50）值显著降低一半，克隆生成、迁移和侵袭能力显著降低，凋亡细胞比例显著增加。Western blot分析显示，与亲本细胞相比，A549和PC-9耐药细胞ZNF516表达下调，ABCC5表达上调。免疫荧光分析显示，与PBS组相比，HA-mEXO处理降低了A549和PC-9耐药细胞中ABCC5的表达，而HA-mEXO和ZNF516敲低共同处理未显示ABCC5表达显著变化。结论：HA-mEXO携带ZNF516抑制ABCC5的表达，从而增强A549和PC-9 LAUD耐药细胞对PMX的敏感性。

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引用次数: 0

[Advances in Antibody-drug Conjugates for Non-small Cell Lung Cancer  after Resistance to First-line Therapy]. [一线治疗耐药后非小细胞肺癌抗体-药物结合物的进展 ]。

Q4 Medicine

中国肺癌杂志

Pub Date : 2025-09-20 DOI: 10.3779/j.issn.1009-3419.2025.101.14

Honglin Li, Yawan Jing, Jiayi Sun, Jing Xu, Yalun Li

Antibody-drug conjugate (ADC), a novel class of antineoplastic agents, combines tumor-specific targeting with potent cytotoxic activity. In recent years, ADC has achieved notable advances in the treatment of non-small cell lung cancer (NSCLC), particularly within therapeutic sequencing after failure of first-line therapy or the emergence of resistance. This paper will systematically review the efficacy and safety evidence of representative ADC in NSCLC, and further to discuss progress and challenges in ADC structural optimization, toxicity management, biomarker identification, and combination strategies, aiming to provide a comprehensive theoretical foundation and practical reference for clinical practice and future research. .

抗体-药物偶联物（ADC）是一类新型的抗肿瘤药物，结合了肿瘤特异性靶向和有效的细胞毒性活性。近年来，ADC在治疗非小细胞肺癌（NSCLC）方面取得了显著进展，特别是在一线治疗失败或出现耐药性后的治疗测序方面。本文将系统综述具有代表性的ADC治疗NSCLC的疗效和安全性证据，并进一步探讨ADC在结构优化、毒性管理、生物标志物鉴定、联合用药策略等方面的进展和挑战，旨在为临床实践和未来的研究提供全面的理论基础和实践参考。

引用次数: 0

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