气腔扩散对早期非小细胞肺癌亚肺叶切除影响的研究进展

彭岚, 唐东昕, 杨柱, 吴娇, 李高, 杨兵, 罗竹敏, 夏子寒, 徐家栋, 吴文宇

彭岚, 唐东昕, 杨柱, 吴娇, 李高, 杨兵, 罗竹敏, 夏子寒, 徐家栋, 吴文宇. 气腔扩散对早期非小细胞肺癌亚肺叶切除影响的研究进展[J]. 中国肿瘤临床, 2025, 52(1): 34-39. DOI: 10.12354/j.issn.1000-8179.2025.20241518
引用本文: 彭岚, 唐东昕, 杨柱, 吴娇, 李高, 杨兵, 罗竹敏, 夏子寒, 徐家栋, 吴文宇. 气腔扩散对早期非小细胞肺癌亚肺叶切除影响的研究进展[J]. 中国肿瘤临床, 2025, 52(1): 34-39. DOI: 10.12354/j.issn.1000-8179.2025.20241518
Lan Peng, Dongxin Tang, Zhu Yang, Jiao Wu, Gao Li, Bing Yang, Zhumin Luo, Zihan Xia, Jiadong Xu, Wenyu Wu. Research progress on the effect of tumor spread through air spaces in sublobar resection for early-stage non-small cell lung cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2025, 52(1): 34-39. DOI: 10.12354/j.issn.1000-8179.2025.20241518
Citation: Lan Peng, Dongxin Tang, Zhu Yang, Jiao Wu, Gao Li, Bing Yang, Zhumin Luo, Zihan Xia, Jiadong Xu, Wenyu Wu. Research progress on the effect of tumor spread through air spaces in sublobar resection for early-stage non-small cell lung cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2025, 52(1): 34-39. DOI: 10.12354/j.issn.1000-8179.2025.20241518

气腔扩散对早期非小细胞肺癌亚肺叶切除影响的研究进展

基金项目: 本文课题受贵州省高等学校中医药民族医药防治肿瘤医学转化工程研究中心(编号:黔教技037号)、贵州省科技计划项目(编号:黔科合基础-ZK一般498,黔科合基础-ZK一般487,黔科合支撑一般095)、贵州省中医肿瘤传承与科技创新人才基地(编号:黔人领发3号)、贵州省高层次创新型人才培养计划(百层次)(编号:黔科合人才4032号)、贵州省杨柱“中医肿瘤学”研究生导师工作室(编号:黔教研合GZS字08)和中医肿瘤学研究生工作站(编号:黔教研合JYSZ字018)资助
详细信息
    作者简介:

    彭岚: 专业方向为中医药防治肿瘤的基础与临床研究

    通讯作者:

    吴文宇 1933208119@qq.com

Research progress on the effect of tumor spread through air spaces in sublobar resection for early-stage non-small cell lung cancer

Funds: This work was supported by the Guizhou Higher Education Traditional Chinese Medicine and Ethnic Medicine Cancer Prevention and Treatment Translational Medicine Research Center (No. Qianjiaoji 037), the Guizhou Science and Technology Program (Nos. QKHJC-ZK General 498, QKHJC-ZK General 487, and QKHZC General 095), Guizhou Traditional Chinese Medicine Oncology Inheritance and Technology Innovation Talent Base (No. Qianrenlingfa 3), Guizhou High-Level Innovative Talent Training Program (Hundred-Level) (No. QKHRC 4032), Guizhou Province Yang Zhu "Traditional Chinese Medicine Oncology" Graduate Advisor Studio (No. Qianjiaoyanhe GZS 08), and Graduate Workstation for Traditional Chinese Medicine Oncology (No. Qianjiaoyanhe JYSZ 018)
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  • 摘要:

    非小细胞肺癌(non-small cell lung cancer, NSCLC)是全球最常见且致命的恶性肿瘤之一,早期NSCLC以手术切除为主要治疗手段。肿瘤经气腔扩散(spread through air spaces, STAS)是一种肿瘤向肺部气腔扩散的新型传播模式,其与亚肺叶切除术后的发生、复发和远处转移密切相关,使其成为手术方式选择和预后评估中至关重要的考虑因素。STAS阳性患者的术后复发率显著高于STAS阴性患者,其分子机制涉及肿瘤微环境的重塑、特异性基因突变及上皮-间质转化等过程。包括计算机断层扫描(CT)和正电子发射断层扫描/CT 在内的影像技术已显示出术前预测 STAS 的潜力,但其准确性和可操作性仍有待提升。本文综述了STAS的定义、病理特征及相关机制,重点探讨STAS阳性患者的手术方式选择及其在早期NSCLC亚肺叶切除术后癌症复发中的作用,并提出未来研究方向,包括优化STAS的术前诊断方法、探索分子靶向治疗以及建立基于影像学的精准预测模型。

    Abstract:

    Non-small cell lung cancer (NSCLC) is one of the most common and deadly malignant tumors worldwide, with surgical resection being the primary treatment for early-stage NSCLC. Tumor spread through air spaces (STAS) is a novel pattern of tumor dissemination into the air spaces in the lung. Its occurrence after sublobar resection is closely associated with recurrence and distant metastasis, making its consideration a vital factor in surgical strategy selection and prognostic evaluation. Patients with STAS-positive status exhibit significantly higher postoperative recurrence rates than do STAS-negative patients, with molecular mechanisms involving tumor microenvironment remodeling, specific genetic mutations, and epithelial-mesenchymal transition (EMT). Imaging techniques including computed tomography (CT) and positron emission tomography/CT have shown potential for preoperative STAS prediction, although their accuracy and practicality require improvement. This paper reviews the definition, pathological characteristics, and related mechanisms of STAS, with a focus on surgical approach selection for STAS-positive patients and its role in cancer recurrence after sublobar resection of early-stage NSCLC. Future research directions include optimization of preoperative diagnostic methods for STAS, exploration of molecular targeted therapies, and development of imaging-based precision prediction models.

  • 癌症是全球主要的死亡原因之一[1-2],其中肺癌的发病率和死亡率最高,非小细胞肺癌(non-small cell lung cancer, NSCLC)占所有肺癌病例的80%~85%。近年来,中国肺癌的发病率持续上升,NSCLC的比例也逐年增加。尽管医疗技术不断发展,但早期NSCLC的主要治疗方法仍为手术切除,尤其是亚肺叶切除(肺段切除和楔形切除),这有助于最大限度地保留肺组织、保护肺功能及改善患者的预后。然而,亚肺叶切除术后复发和转移的风险远高于肺叶切除,这可能与气腔传播(spread through air spaces,STAS)有关。STAS是2015年世界卫生组织(WHO)提出的新概念,是指肿瘤细胞通过肺组织的气腔扩散到周围组织,而非血管或淋巴管传播[3]。STAS作为一种新型的肿瘤扩散机制,与术后复发密切相关,已成为影响早期NSCLC预后的关键性因素。STAS在肺鳞癌和肺腺癌中最为常见,其加剧肿瘤的侵袭性,显著增加了早期NSCLC患者术后复发和远处转移的风险,且相较于STAS阴性患者有更高的5 年死亡率。

    因此,如何精确评估STAS状态及优化治疗策略,已成为当前临床的关键问题,特别是在早期 NSCLC术后管理和随访中,对于STAS阳性患者应更加关注转移的风险,以减少复发和转移的发生。

    STAS近年来在肺癌病理学领域引起了广泛关注。2015年首次提出STAS的概念,指肿瘤细胞通过气腔扩散至肿瘤边缘以外的现象,表现为微乳头簇、实性巢或单个细胞等形式的肿瘤细胞脱离原发肿瘤,经肺组织气腔向周围扩散[4]。这一发现突破了传统对肺癌局部扩散机制的认知,使STAS成为继血管、淋巴管浸润和胸膜侵犯之后又一重要侵袭模式。STAS主要包括3种形态学模式:1)微乳头状细胞簇,其结构缺乏中央纤维血管核心,部分呈环状分布于气腔内;2)实体癌巢或肿瘤岛,表现为充满气穴的实体肿瘤细胞团;3)单个肿瘤细胞,自由漂浮于空气腔隙中[5]。据此不同研究者对STAS的形态特征及分布范围提出了多种分级体系:Uruga等[6]根据STAS肿瘤细胞数量将其分为无STAS、低STAS(1~4个细胞或细胞簇)及高STAS(≥5个细胞);Warth等[7]则依据STAS的扩散距离分为限制性STAS(3个肺泡层以内)和广泛性STAS(超过3个肺泡层)。Han等[8]根据STAS细胞簇与主肿瘤之间的距离,将距离<2 500 μm(1个×10物镜的视野)定义为STAS Ⅰ级,距离>2 500 μm(一个×10物镜的视野)定义为STAS Ⅱ级。这些分级体系为STAS的临床诊断和预后评估提供了重要参考。另外,Kadota等[9]发现,STAS细胞通常扩散至肿瘤边缘约1.7 cm的范围,这一距离对手术切缘的设计具有重要指导意义。尽管STAS最初被认为是肺腺癌的特异性扩散模式,近年研究表明STAS同样在肺鳞癌中具有显著发生率,且有更高的侵袭性及更差的生存预后。

    总体而言,STAS的提出不仅丰富了肺癌扩散机制的理论,同时对术后复发风险的评估及手术策略的选择提供了新方向。但其机制尚未完全阐明,在不同病理亚型中的特征及临床意义仍需进一步探索。

    STAS作为一种新型的肿瘤扩散模式,在NSCLC术后复发和转移中的重要作用逐渐引起关注。STAS肿瘤细胞能够脱离原发肿瘤,通过气腔迁移至周围组织,而非传统的血管或淋巴管途径。这一过程涉及气道播散、肿瘤微环境及分子机制的调控等。

    气道播散是STAS核心机制之一,手术或标本处理过程中可能破坏气道结构,为肿瘤细胞迁移提供了路径,从而增加局部复发风险。研究发现,尽管不同的活检方法(经皮穿刺、支气管镜检和非穿刺)对STAS的发生率无显著差异,但在接受亚肺叶切除的STAS阳性患者中,活检操作显著提高了复发风险和肺癌特异性死亡率,而在接受肺叶切除的STAS阳性患者中却无明显差异。这提示,活检操作可能通过机械干扰导致肿瘤细胞脱落至气腔内,而亚肺叶切除术中可能由于切缘设计不足,未能完全切除含有肿瘤细胞的组织,从而增加复发风险[10-11]。但Blaauwgeers等[12]提出“通过刀表面扩散”假说,认为该现象是由标本切割操作不当细胞沿刀片扩散所形成的“漂浮”细胞团,但大量研究表明STAS是真实存在的肿瘤扩散模式,而非单纯的技术伪影,可通过三维成像特征排除伪影可能性:1)机械作用引起的肿瘤漂浮物通常随机分布在组织切片的边缘或切片平面之外;2)肿瘤细胞簇的锯齿形边缘可能由切割刀的边缘所致;3)孤立的肿瘤簇与肿瘤之间有一定间隔,而非连续扩展;4)肿瘤细胞的线状条带已从肺泡壁脱离等[13]。Yagi等[14]利用3D重建和多重免疫荧光技术观察到,STAS细胞能够通过肺泡气腔扩散并重新附着于周围组织,也进一步证明STAS真实性。

    STAS的气道播散机制对术后复发的影响逐渐清晰,尤其在亚肺叶切除术中。未来研究应聚焦于如何阻断气腔迁移路径,优化术前穿刺策略,制定更合理的术中切缘设计方案,规范标本处理流程,从而降低术后局部复发风险,为STAS阳性患者制定更精准的手术和综合治疗方案。

    肿瘤微环境对STAS细胞的存活和扩散起着重要作用,其动态变化为STAS细胞的迁移和种植提供了有利条件。研究表明,STAS细胞能够在肺泡内漂浮,并重新附着于肺泡壁及毛细血管壁。Huttala等[15]还发现癌细胞能在去细胞化的毛细血管结构上形成“网络”和“簇”两种不同的生长模式,在“网络”模式还能吸引脱落的肿瘤细胞使其向内转移,促进肿瘤扩散。这表明,肿瘤微环境中的血管结构可能为其提供粘附场所,促进其扩散。此外,Yagi等[14]提出的“动态血管共选择”假说也指出,STAS细胞更倾向于依附于现有毛细血管结构,而非通过诱导新生血管实现扩散。这暗示传统抗血管生成疗法可能对STAS阳性患者疗效有限,这也对术中切缘设计具有重要意义,术中需关注肿瘤周围毛细血管的分布,以减少STAS细胞的附着和播散风险。微环境中的细胞因子(如vascular endothelial growth factor,VEGF)和基质金属蛋白酶(matrix metalloproteinases,MMPs)在STAS形成中也起着重要作用。MMPs通过降解细胞外基质和基底膜,增强STAS细胞的侵袭性,促进局部复发和远处转移[16-17]。此外,STAS与上皮间质转化(epithelial-mesenchymal transition,EMT)密切相关。EMT通过转录因子(如Twist、Slug)诱导肿瘤细胞失去E-钙粘蛋白,降低其粘附性,使得肿瘤细胞从原发性肿瘤中逃逸并增强其迁移能力。STAS细胞在由中央向边缘的迁移过程中也经历了明显的EMT变化,且EMT还有助于非肿瘤干细胞获得肿瘤干细胞的特性,促进其自我更新和分化并增强治疗抗性[18]

    免疫微环境在STAS的形成和扩散中同样重要,肿瘤细胞诱导下中性粒细胞可释放双链DNA、组蛋白及弹性蛋白酶等形成中性粒细胞胞外诱捕网,可捕获循环肿瘤细胞并加速血管生成,从而促进STAS细胞的转移[19]。此外,PD-L1的高表达与STAS显著相关,虽机制尚不完全明确,但PD-L1作为肿瘤免疫逃逸的关键因子,可能为STAS细胞的扩散提供支持[20-21]

    综合来看,肿瘤微环境通过血管结构支持、细胞因子调控、免疫保护及EMT的驱动等途径,为STAS细胞的形成和扩散提供基础。但传统抗血管生成治疗对STAS阳性患者的疗效可能有限,未来研究应进一步聚焦于微环境的综合调控策略,如联合使用EMT抑制剂、MMPs抑制剂、PD-L1靶向免疫以及中性粒细胞功能调控药物,以实现对STAS扩散的精准干预改善患者预后。

    STAS复杂的分子机制涉及基因突变、表观遗传调控及多条信号通路的参与。STAS阳性可能与花生四烯酸代谢及二十烷类信号通路的异常激活有关,这种激活通过上调前列腺素合成酶增强肿瘤细胞的迁移和侵袭性,同时局部前列腺素2过表达可激活PD-1/PD-L1信号通路,抑制T淋巴细胞的增殖和活化,促进肿瘤细胞免疫逃逸[22]。在基因方面[23],EGFR、TP53、KARS、ALK和ROS1是STAS阳性肺腺癌中最常见突变基因,其中,KRAS基因突变更为常见,且与更短的无病生存期和无复发生存期密切相关。但不同研究对这一关联的结论存在分歧。可能与肿瘤亚型及患者个体而异。

    表观遗传调控在STAS的发生和发展中也起重要作用,特定长链非编码RNA通过调控EMT相关基因的表达,促进STAS细胞的扩散和远端附着。此外,STAS细胞常伴随E-cadherin低表达,这一表型与EMT密切相关,进一步解释了其高迁移性[24]。转录因子和细胞信号通路可能在STAS调控中发挥关键作用,转移相关蛋白1的高表达和PI3K/AKT及Wnt/β-catenin信号通路的激活与STAS细胞骨架重塑,增殖和侵袭性密切相关,使得STAS阳性患者预后更差[25]

    总体而言,STAS的分子机制涉及多维度、多层次的复杂网络,其驱动因素因患者个体及肿瘤亚型而异。未来的研究应结合单细胞测序、空间组学和多维分子分析,进一步揭示STAS调控机制及其潜在的治疗靶点。

    STAS的发现为早期NSCLC患者的术后管理与预后评估提供了新的视角。尤其对手术策略、术后辅助治疗及术前评估技术的开发具有重要意义。

    在NSCLC的治疗中,亚肺叶切除术(如楔形切除术和肺段切除术)因保留更多肺组织,在术后肺功能恢复和生活质量改善方面具有显著优势,特别适用于早期NSCLC患者。然而,STAS阳性患者在接受亚肺叶切除术后局部复发和远处转移的风险显著高于STAS阴性患者[26],且复发风险较肺叶切除更高。Ikeda等[27]发现,肺段切除在STAS阳性Ⅰ期肺腺癌患者中的预后与肺叶切除相当,而楔形切除则更有高的复发风险,这可能与其切缘较窄,难以完全去除STAS扩散区域的肿瘤细胞有关。Han等[8]也指出,STAS细胞扩散范围较大者应选择肺叶切除术,以彻底清除STAS扩散区域。另外对于Ⅰ期肺腺癌患者低侵袭性亚型(如非典型腺瘤样增生、原位腺癌和微浸润腺癌),亚肺叶切除术是合理的选择;而对于侵袭性较强的浸润型肺腺癌,肺叶切除术则更能降低复发和转移的风险。

    对既往文献回顾,使用“STAS”、“肺肿瘤(lung neoplasms)”、“小细胞肺癌(small cell lung carcinoma)”和“非小细胞肺癌(carcinoma, non-small-cell lung)”等关键词进行检索,共筛选出18篇[68-92528-41]关于STAS与肺癌术后复发、转移及预后的病例研究(表1)。其中5篇关于肺叶切除与亚肺叶切除(楔形切除为主)(表2),另外2篇关于肺叶切除与亚肺叶切除(肺段切除为主)(表3)。结果显示,无论是肺叶切除还是亚肺叶切除,STAS阳性患者的5年无复发转移率和5年生存率均显著低于STAS阴性患者。进一步分析发现,STAS阳性患者的5年无复发转移率呈现以下趋势:肺段切除或肺叶切除>楔形切除。这表明,亚肺叶切除,特别是楔形切除,对于STAS阳性患者的预后较差,进一步证实手术方式对患者预后有重大影响。总的来说,STAS的存在对NSCLC患者的手术策略和术后管理提出了更高要求。优化手术方式和切缘设计对改善预后至关重要。未来的研究应进一步探索STAS的扩散特征与手术策略之间的匹配关系,为精准治疗提供依据。

    表  1  STAS对肺癌术后复发及预后的影响
    文献 总数 分期 病理 STAS
    STAS(+)/STAS(−)
    5年生存率
    STAS(+)/STAS(−)
    5年无复发率
    STAS(+)/STAS(−)
    Toyokawa等[28] 82 ADC 31/51 79.2%/92.7% 69.2%/96.7%
    Uruga等[6] 208 ADC 99/109 85.0%/98.0%
    Kadota等[9] 411 ADC 155/256 76.6%/84.7% 87.4%/93.7%
    Shiono等[29] 514 104/410 68.4%/89.1% 78.9%/93.4%
    Kagimoto等[30] 609 ADC 293/316 72.3%/91.3%
    Eguchi等[31] 698 ADC 276/422 88.0%/96.0% 72.6%/92.5%
    Bains等[32] 909 ADC 317/592 54.6%/91.2%
    Shiono等[33] 848 139/709 65.4%/89.0%
    Han等[8] 870 ADC 237/623 93.6%/98.2% 86.3%/97.8%
    Chae等[34] 115 ADC 20/95 82.6%/98.5%
    Lv等[35] 3 328 ADC 600/2728 90.8%/95.5% 89.5%/93.3%
    Jung等[36] 506 ADC 204/302 79.3%/93.3%
    Shiono等[37] 318 47/271 62.7%/91.1% 54.4%/87.8%
    Toyokawa等[38] 276 ADC 155/123 91.3%/98.3% 71.7%/89.5%
    Liu等[25] 208 Ⅰ~Ⅲ ADC 107/101 30.0%/75.2% 21.6%/63.8%
    Lu等[39] 445 Ⅰ~Ⅲ ASC 227/218 34.0%/48.0%
    Kadota等[40] 735 Ⅰ~Ⅳ 247/488 61.0%/93.0% 48.0%/97.0%
    Yanagawa等[41] 120 SCC 24/96 50.2%/71.4% 37.4%/68.4%
      100 Ⅱ~Ⅲ SCC 18/82 36.4%/51.5% 39.2%/48.9%
    下载: 导出CSV 
    | 显示表格
    表  2  肺叶切除与亚肺叶切除(楔形切除为主)STAS患者的5年无复发生存率
    文献 总数 分期 肺叶切除/亚肺叶切除(楔形切除为主) 5年无复发率[STAS(+)/STAS(−)]
    人数 STAS(+) 肺叶切除 亚肺叶切除(楔形切除为主)
    Kadota等[9] 411 I 291/120 109/46 87.3%/90.5% 57.4%/89.1%
    Eguchi等[31] 698 I 349/349 141/135 84.0%/94.0% 61.0%/91.0%
    Bains等[32] 909 I 557/352 119/126 84.0%/92.0% 58.0%/90.0%
    Han等[8] 870 I 648/222 204/33 86.2%/97.2% 86.2%/98.9%
    Chae等[34] 115 I 88.9%/98.6% 62.4%/97.9%
    下载: 导出CSV 
    | 显示表格
    表  3  肺叶切除与亚肺叶切除(肺段切除为主)STAS患者的5年无复发生存率
    文献 总数 分期 肺叶/亚肺叶切除(肺段切除为主) 5年无复发率[STAS(+)/STAS(−)]
    人数 STAS(+) 肺叶切除 亚肺叶切除(肺段切除为主)
    Shiono等[29] 514 I 329/185 73/31 64.5%/89.6% 83.6%/95.3%
    Kagimoto等[30] 609 I 348/216 186/107 68.2%/90.2% 81.3%/93.0%
    下载: 导出CSV 
    | 显示表格

    STAS的存在不仅影响手术策略,还突显了术后辅助治疗的重要性。对于Ⅰ期STAS阳性NSCLC患者,术后辅助化疗可显著提高无复发生存期和总生存期[42]。Xie等[43]也发现,对高复发风险的Ⅰ期STAS阳性患者,辅助化疗尤其能显著延长其术后生存时间。但辅助治疗的具体获益情况可能因术式及STAS分级的不同而有所差异。研究显示,接受亚肺叶切除的STAS阳性患者对辅助化疗的反应优于肺叶切除[43]。这说明,辅助治疗方案应结合STAS的特征和患者术式、病理分级进行个性化调整,以实现最佳的治疗效果。

    STAS的术后病理诊断虽然是金标准,但对术前和术中指导意义有限。近年来,影像学技术的发展为STAS的术前预测提供了新的可能性。CT和PET-CT等可通过分析病灶的侵袭性特征(如胸膜凹陷、分叶和毛刺)可初步判断STAS的可能性,而其他CT特征(如血管会聚、支气管充气征和边界不清的外周混浊)差异较小[44],此外STAS阳性肿瘤常伴有较高的代谢体积和不规则边缘。此外,人工智能算法在影像数据中的应用为提高预测的敏感性和特异性供了新途径,有望为手术方式的选择和术前决策提供更科学的依据。尽管术中快速冰冻切片的灵敏度有限,但结合术前影像特征,可为切缘设计和手术方式调整提供重要参考。

    STAS的存在使得NSCLC的术后管理更加复杂,需多学科协作,从手术策略、术后辅助治疗到术前影像评估,共同制定个体化的治疗方案。未来应开展多中心、大样本研究,验证不同治疗策略对STAS阳性患者的长期生存获益情况。此外,STAS特异性的靶向治疗研发仍处于初级阶段,需进一步加强对分子机制的研究以实现更精准的治疗。

    STAS作为一种新型的肿瘤扩散模式,在早期NSCLC患者中显著影响术后复发和转移。本文综述了STAS的病理特征、临床表现及分子机制,明确其在亚肺叶切除术后评估中的关键作用。STAS阳性肿瘤具有更高侵袭性和复发风险,尤其是亚肺叶切除术后远期生存率显著降低。因此,STAS的准确评估和分层管理对于制定更有效的治疗策略至关重要。尽管目前研究已经取得一定进展,但仍存在以下挑战:1)量化标准缺乏统一,不同研究间存在异质性;2)STAS的发生机制与肿瘤微环境、基因突变的具体关联仍需进一步探索;3)目前的术前和术中评估方法在灵敏度和特异性上尚未满足临床需求;4)STAS阳性的特异性治疗策略缺乏,分子靶向或辅助治疗仍处于探索阶段。

    未来研究方向应集中在以下方面:1)多中心、大样本研究STAS对早期NSCLC亚肺叶切除的影响,并明确其量化分级对临床决策的指导意义;2)利用单细胞测序、空间多组学等前沿技术,深入解析STAS的分子机制和肿瘤微环境的动态交互,为发现新型治疗靶点提供依据;3)开发术前无创预测模型,将高分辨率CT、PET-CT等影像技术与人工智能算法相结合,提高STAS的术前预测准确性;4)优化手术方式及术后辅助治疗,探索潜在的分子靶向治疗策略;5)整合多学科力量,对STAS阳性患者开展更精准的诊疗与管理。总之,STAS阳性在NSCLC的诊治领域具有重要的临床价值和研究前景。未来的深入研究不仅有助于提升对STAS的认识,还将为肺癌患者的个体化治疗和精准医学提供有力支持。

  • 表  1   STAS对肺癌术后复发及预后的影响

    文献 总数 分期 病理 STAS
    STAS(+)/STAS(−)
    5年生存率
    STAS(+)/STAS(−)
    5年无复发率
    STAS(+)/STAS(−)
    Toyokawa等[28] 82 ADC 31/51 79.2%/92.7% 69.2%/96.7%
    Uruga等[6] 208 ADC 99/109 85.0%/98.0%
    Kadota等[9] 411 ADC 155/256 76.6%/84.7% 87.4%/93.7%
    Shiono等[29] 514 104/410 68.4%/89.1% 78.9%/93.4%
    Kagimoto等[30] 609 ADC 293/316 72.3%/91.3%
    Eguchi等[31] 698 ADC 276/422 88.0%/96.0% 72.6%/92.5%
    Bains等[32] 909 ADC 317/592 54.6%/91.2%
    Shiono等[33] 848 139/709 65.4%/89.0%
    Han等[8] 870 ADC 237/623 93.6%/98.2% 86.3%/97.8%
    Chae等[34] 115 ADC 20/95 82.6%/98.5%
    Lv等[35] 3 328 ADC 600/2728 90.8%/95.5% 89.5%/93.3%
    Jung等[36] 506 ADC 204/302 79.3%/93.3%
    Shiono等[37] 318 47/271 62.7%/91.1% 54.4%/87.8%
    Toyokawa等[38] 276 ADC 155/123 91.3%/98.3% 71.7%/89.5%
    Liu等[25] 208 Ⅰ~Ⅲ ADC 107/101 30.0%/75.2% 21.6%/63.8%
    Lu等[39] 445 Ⅰ~Ⅲ ASC 227/218 34.0%/48.0%
    Kadota等[40] 735 Ⅰ~Ⅳ 247/488 61.0%/93.0% 48.0%/97.0%
    Yanagawa等[41] 120 SCC 24/96 50.2%/71.4% 37.4%/68.4%
      100 Ⅱ~Ⅲ SCC 18/82 36.4%/51.5% 39.2%/48.9%
    下载: 导出CSV

    表  2   肺叶切除与亚肺叶切除(楔形切除为主)STAS患者的5年无复发生存率

    文献 总数 分期 肺叶切除/亚肺叶切除(楔形切除为主) 5年无复发率[STAS(+)/STAS(−)]
    人数 STAS(+) 肺叶切除 亚肺叶切除(楔形切除为主)
    Kadota等[9] 411 I 291/120 109/46 87.3%/90.5% 57.4%/89.1%
    Eguchi等[31] 698 I 349/349 141/135 84.0%/94.0% 61.0%/91.0%
    Bains等[32] 909 I 557/352 119/126 84.0%/92.0% 58.0%/90.0%
    Han等[8] 870 I 648/222 204/33 86.2%/97.2% 86.2%/98.9%
    Chae等[34] 115 I 88.9%/98.6% 62.4%/97.9%
    下载: 导出CSV

    表  3   肺叶切除与亚肺叶切除(肺段切除为主)STAS患者的5年无复发生存率

    文献 总数 分期 肺叶/亚肺叶切除(肺段切除为主) 5年无复发率[STAS(+)/STAS(−)]
    人数 STAS(+) 肺叶切除 亚肺叶切除(肺段切除为主)
    Shiono等[29] 514 I 329/185 73/31 64.5%/89.6% 83.6%/95.3%
    Kagimoto等[30] 609 I 348/216 186/107 68.2%/90.2% 81.3%/93.0%
    下载: 导出CSV
  • [1]

    Bray F, Laversanne M, Weiderpass E, et al. The ever-increasing importance of cancer as a leading cause of premature death worldwide[J]. Cancer, 2021, 127(16):3029-3030. DOI: 10.1002/cncr.33587

    [2]

    Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020[J]. Chin Med J, 2021, 134(7):783-791. DOI: 10.1097/CM9.0000000000001474

    [3]

    Fan L, He P. Research progress on spread through air spaces of lung cancer[J]. Zhongguo Fei Ai Za Zhi, 2022, 25(1):54-60.

    [4]

    Shih AR, Mino-Kenudson M. Updates on spread through air spaces (STAS) in lung cancer[J]. Histopathology, 2020, 77(2):173-180. DOI: 10.1111/his.14062

    [5] 丁会珍,杨峰燕,金贻铎,等.气道播散与肺腺癌临床病理危险因素相关性分析[J].诊断病理学杂志,2024,31(1):1-4. DOI: 10.3969/j.issn.1007-8096.2024.01.001
    [6]

    Uruga H, Fujii T, Fujimori S, et al. Semiquantitative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas[J]. J Thorac Oncol, 2017, 12(7):1046-1051. DOI: 10.1016/j.jtho.2017.03.019

    [7]

    Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma[J]. Am J Surg Pathol, 2015, 39(6):793-801. DOI: 10.1097/PAS.0000000000000409

    [8]

    Han YB, Kim H, Mino-Kenudson M, et al. Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer[J]. Mod Pathol, 2021, 34(3):549-561. DOI: 10.1038/s41379-020-00709-2

    [9]

    Kadota K, Nitadori JI, Sima CS, 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]. J Thorac Oncol, 2015, 10(5):806-814. DOI: 10.1097/JTO.0000000000000486

    [10]

    Lee GY, Chung JH, Cho S, et al. Impact of preoperative diagnostic biopsy procedure on spread through airspaces and related outcomes in resected stage Ⅰ non-small cell lung cancer[J]. Chest, 2022, 162(5):1199-1212. DOI: 10.1016/j.chest.2022.05.002

    [11]

    Ding Y, Li JZ, Li X, et al. Impact of preoperative biopsy on tumor spread through air spaces in stage Ⅰ non-small cell lung cancer: a propensity score-matched study[J]. BMC Pulm Med, 2022, 22(1):293. DOI: 10.1186/s12890-022-02090-z

    [12]

    Blaauwgeers H, Russell PA, Jones KD, et al. Pulmonary loose tumor tissue fragments and spread through air spaces (STAS): Invasive pattern or artifact? A critical review[J]. Lung Cancer, 2018, 123:107-111. DOI: 10.1016/j.lungcan.2018.07.017

    [13]

    Gross DJ, Hsieh MS, Li Y, et al. Spread through air spaces (STAS) in non-small cell lung carcinoma: evidence supportive of an in vivo phenomenon[J]. Am J Surg Pathol, 2021, 45(11):1509-1515. DOI: 10.1097/PAS.0000000000001788

    [14]

    Yagi Y, Aly RG, Tabata K, et al. Three-dimensional histologic, immunohistochemical, and multiplex immunofluorescence analyses of dynamic vessel co-option of spread through air spaces in lung adenocarcinoma[J]. J Thorac Oncol, 2020, 15(4):589-600 DOI: 10.1016/j.jtho.2019.12.112

    [15]

    Huttala O, Loreth D, Staff S, et al. Decellularized in vitro capillaries for studies of metastatic tendency and selection of treatment[J]. Biomedicines, 2022, 10(2):271. DOI: 10.3390/biomedicines10020271

    [16] 叶其淼,李建强.基质金属蛋白酶9在非小细胞肺癌中的研究进展[J].中国医药,2023,18(1):131-134.
    [17] 王朝鑫.血清CYFRA21-1、NSE、VEGF水平联合检测对肺癌患者淋巴结转移的诊断价值[J].中国民康医学,2024,36(17):127-129,133. DOI: 10.3969/j.issn.1672-0369.2024.17.038
    [18]

    Lei ZN, Teng QX, Koya J, et al. The correlation between cancer stem cells and epithelial-mesenchymal transition: molecular mechanisms and significance in cancer theragnosis[J]. Front Immunol, 2024, 15:1417201. DOI: 10.3389/fimmu.2024.1417201

    [19]

    Wang Y, Liu F, Chen L, et al. Neutrophil extracellular traps (NETs) promote non-small cell lung cancer metastasis by suppressing lncRNA MIR503HG to activate the NF-κB/NLRP3 inflammasome pathway[J]. Front Immunol, 2022, 13:867516. DOI: 10.3389/fimmu.2022.867516

    [20]

    Wang J, Yao YS, Tang DF, et al. An individualized nomogram for predicting and validating spread through air space (STAS) in surgically resected lung adenocarcinoma: a single center retrospective analysis[J]. J Cardiothorac Surg, 2023, 18(1):337. DOI: 10.1186/s13019-023-02458-0

    [21]

    Wang S, Shou HK, Wen HY, et al. An individual nomogram can reliably predict tumor spread through air spaces in non-small-cell lung cancer[J]. BMC Pulm Med, 2022, 22(1):209. DOI: 10.1186/s12890-022-02002-1

    [22] 袁野,庄金宝,石旭,等.PGE2对非小细胞肺癌组织浸润T淋巴细胞中PD-1表达的影响及其机制[J].吉林大学学报(医学版),2021,47(2):249-256.
    [23]

    Shen FF, Wu XY, Geng J, et al. Prognostic factors for resected invasive mucinous lung adenocarcinoma: a systematic review and meta-analysis[J]. BMC Cancer, 2024, 24(1):1317. DOI: 10.1186/s12885-024-13068-x

    [24]

    Liu JH, Li DP, Luo H, et al. Circular RNAs: The star molecules in cancer[J]. Mol Aspects Med, 2019, 70:141-152. DOI: 10.1016/j.mam.2019.10.006

    [25]

    Liu YY, Chen DL, Qiu X, et al. Relationship between MTA1 and spread through air space and their joint influence on prognosis of patients with stage Ⅰ-Ⅲ lung adenocarcinoma[J]. Lung Cancer, 2018, 124:211-218. DOI: 10.1016/j.lungcan.2018.07.040

    [26]

    Nakanishi R, Okuda K, Yokota K, et al. Complex video-assisted thoracoscopic surgery lobectomy for locally advanced lung cancer: a prospective feasibility study[J]. Surg Today, 2022, 52(11):1582-1590. DOI: 10.1007/s00595-022-02491-x

    [27]

    Ikeda T, Kadota K, Go T, et al. Segmentectomy provides comparable outcomes to lobectomy for stage ⅠA non-small cell lung cancer with spread through air spaces[J]. Semin Thorac Cardiovasc Surg, 2023, 35(1):156-163. DOI: 10.1053/j.semtcvs.2022.02.001

    [28]

    Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in early-stage lung adenocarcinomas undergoing limited resection[J]. Thorac Cancer, 2018, 9(10):1255-1261. DOI: 10.1111/1759-7714.12828

    [29]

    Shiono S, Endo M, Suzuki K, et al. Spread through air spaces is a prognostic factor in sublobar resection of non-small cell lung cancer[J]. Ann Thorac Surg, 2018, 106(2):354-360. DOI: 10.1016/j.athoracsur.2018.02.076

    [30]

    Kagimoto A, Tsutani Y, Kushitani K, et al. Segmentectomy vs lobectomy for clinical stage IA lung adenocarcinoma with spread through air spaces[J]. Ann Thorac Surg, 2021, 112(3):935-943. DOI: 10.1016/j.athoracsur.2020.09.020

    [31]

    Eguchi T, Kameda K, Lu SH, et al. Lobectomy is associated with better outcomes than sublobar resection in spread through air spaces (STAS)-positive T1 lung adenocarcinoma: a propensity score-matched analysis[J]. J Thorac Oncol, 2019, 14(1):87-98. DOI: 10.1016/j.jtho.2018.09.005

    [32]

    Bains S, Eguchi T, Warth A, et al. Procedure-specific risk prediction for recurrence in patients undergoing lobectomy or sublobar resection for small (≤2 Cm) lung adenocarcinoma: an international cohort analysis[J]. J Thorac Oncol, 2019, 14(1):72-86. DOI: 10.1016/j.jtho.2018.09.008

    [33]

    Shiono S, Endo M, Suzuki K, et al. Spread through air spaces in lung cancer patients is a risk factor for pulmonary metastasis after surgery[J]. J Thorac Dis, 2019, 11(1):177-187. DOI: 10.21037/jtd.2018.12.21

    [34]

    Chae M, Jeon JH, Chung JH, et al. Prognostic significance of tumor spread through air spaces in patients with stage ⅠA part-solid lung adenocarcinoma after sublobar resection[J]. Lung Cancer, 2021, 152:21-26. DOI: 10.1016/j.lungcan.2020.12.001

    [35]

    Lv YL, Li SW, Liu ZC, et al. Impact of surgery and adjuvant chemotherapy on the survival of stage Ⅰ lung adenocarcinoma patients with tumor spread through air spaces[J]. Lung Cancer, 2023, 177:51-58. DOI: 10.1016/j.lungcan.2023.01.009

    [36]

    Jung W, Chung JH, Yum S, et al. The differential prognostic impact of spread through air spaces in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor[J]. J Thorac Cardiovasc Surg, 2022, 163(1):277-284. DOI: 10.1016/j.jtcvs.2020.09.098

    [37]

    Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage Ⅰ lung adenocarcinoma[J]. Interact Cardiovasc Thorac Surg, 2016, 23(4):567-572. DOI: 10.1093/icvts/ivw211

    [38]

    Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in resected pathological stage Ⅰ lung adenocarcinoma[J]. Ann Thorac Surg, 2018, 105(6):1655-1663. DOI: 10.1016/j.athoracsur.2018.01.037

    [39]

    Lu SH, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma[J]. J Thorac Oncol, 2017, 12(2):223-234. DOI: 10.1016/j.jtho.2016.09.129

    [40]

    Kadota K, Kushida Y, Kagawa S, et al. Limited resection is associated with a higher risk of locoregional recurrence than lobectomy in stage Ⅰ lung adenocarcinoma with tumor spread through air spaces[J]. Am J Surg Pathol, 2019, 43(8):1033-1041. DOI: 10.1097/PAS.0000000000001285

    [41]

    Yanagawa N, Shiono S, Endo M, et al. Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage I lung squamous cell carcinoma, but not in stage II and III[J]. Lung Cancer, 2018, 120:14-21. DOI: 10.1016/j.lungcan.2018.03.018

    [42]

    Chen DL, Wang XF, Zhang FQ, et al. Could tumor spread through air spaces benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-institutional study[J]. Ther Adv Med Oncol, 2020, 12:1758835920978147.

    [43]

    Xie SN, Liu QY, Han YQ, et al. Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis[J]. Front Oncol, 2022, 12:905958. DOI: 10.3389/fonc.2022.905958

    [44]

    Li HJ, Li LF, Liu YM, et al. Predictive value of CT and 18F-FDG PET/CT features on spread through air space in lung adenocarcinoma[J]. BMC Cancer, 2024, 24(1):434. DOI: 10.1186/s12885-024-12220-x

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出版历程
  • 收稿日期:  2024-11-19
  • 修回日期:  2025-02-03
  • 录用日期:  2025-02-04
  • 刊出日期:  2025-01-14

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