转录组学解析NFIA在HER2阳性乳腺癌脑转移中的作用研究

doi:10.19586/j.2095-2341.2026.0016

生物技术进展 ›› 2026, Vol. 16 ›› Issue (3): 706-718.DOI: 10.19586/j.2095-2341.2026.0016

转录组学解析NFIA在HER2阳性乳腺癌脑转移中的作用研究

董梦洁¹(), 范佩文², 王若峥²^,³()

^1.新疆医科大学附属肿瘤医院，乌鲁木齐 830011
^2.新疆医科大学附属肿瘤医院，新疆肿瘤学重点实验室，乌鲁木齐 830011
^3.新疆维吾尔自治区放射治疗重点临床专科，乌鲁木齐 830011

收稿日期:2026-01-23 接受日期:2026-03-31 出版日期:2026-05-25 发布日期:2026-07-14
通讯作者: 王若峥
作者简介:董梦洁 E-mail: 747637363@qq.com；
基金资助:
中央引导地方科技发展专项资金项目(ZYYD2022B18);新疆维吾尔自治区重点研发计划项目(2022B03019-5)

Transcriptomic Analysis of the Role of NFIA in HER2-positive Breast Cancer Brain Metastasis

Mengjie DONG¹(), Peiwen FAN², Ruozheng WANG²^,³()

^1.Affiliated Cancer Hospital of Xinjiang Medical University，Urumqi 830011，China
^2.Xinjiang Key Laboratory of Oncology，Affiliated Cancer Hospital of Xinjiang Medical University，Urumqi 830011，China
^3.Clinical Key Specialty of Radiotherapy of Xinjiang Uygur Autonomous Region，Urumqi 830011，China

Received:2026-01-23 Accepted:2026-03-31 Online:2026-05-25 Published:2026-07-14
Contact: Ruozheng WANG

摘要/Abstract

摘要：

研究系统探讨了核因子IA（nuclear factor IA, NFIA）在HER2阳性乳腺癌脑转移（breast cancer brain metastasis，BCBM）中的表达特征以及与患者预后的关系，及其在肿瘤微环境（tumor microenvironment，TME）中的潜在作用，旨在为临床干预提供新的治疗靶点。基于多个公共数据库分析了NFIA的表达特点及其与预后的相关性，并结合临床配对样本开展免疫组织化学（immunohistochemistry，IHC）验证。同时，整合公共数据库与自测单细胞转录组数据，对NFIA高表达细胞亚群的功能状态及其微环境通讯特征进行了系统分析。结果显示，NFIA在人表皮生长因子受体2（human epidermal growth factor receptor-2, HER2）阳性BCBM中显著高表达，且其高表达与患者不良预后密切相关。单细胞分析进一步揭示，NFIA高表达的肿瘤上皮细胞表现出显著的基因组不稳定性和高度恶性特征，并伴随侵袭、增殖等肿瘤相关通路的显著激活。此外，NFIA高表达细胞通过调控上皮间质转化等关键信号通路，在肿瘤微环境中发挥重要作用。综上所述，NFIA高表达定义了HER2阳性BCBM中具有高度恶性特征的肿瘤上皮细胞亚群，并通过微环境调控促进肿瘤进展，为HER2阳性乳腺癌脑转移的精准治疗提供了潜在的分子靶点。

关键词: NFIA, HER2阳性乳腺癌脑转移, 单细胞转录组, 肿瘤微环境

Abstract:

This study systematically investigated the expression characteristics of NFIA in HER2-positive breast cancer brain metastasis （BCBM） and its association with patient prognosis， as well as its potential roles in the tumor microenvironment （TME）， aiming to identify novel therapeutic targets. NFIA expression patterns and their prognostic relevance were analyzed using multiple public databases， and immunohistochemistry （IHC） validation was performed on paired clinical samples. Furthermore， by integrating public datasets with our single-cell transcriptomic data， we systematically analyzed the functional states of NFIA-high cell subpopulations and their interactions within the TME. The results demonstrated that NFIA was significantly upregulated in HER2-positive BCBM and that its high expression was closely associated with poor patient prognosis. Single-cell analyses further revealed that NFIA-high tumor epithelial cells exhibited pronounced genomic instability and highly malignant features， accompanied by activation of pathways related to invasion and proliferation. In addition， NFIA-high cells acted as key modulators within the TME by regulating angiogenesis， immune suppression， and extracellular matrix remodeling. Collectively， NFIA high expression defines a highly malignant tumor epithelial cell subpopulation in HER2-positive BCBM and promotes tumor progression through TME remodeling， providing a potential molecular target for precision therapy in HER2-positive breast cancer brain metastasis.

Key words: NFIA, HER2-positive breast cancer brain metastasis, single-cell transcriptome, tumor microenvironment

中图分类号:

Q786

董梦洁, 范佩文, 王若峥. 转录组学解析NFIA在HER2阳性乳腺癌脑转移中的作用研究[J]. 生物技术进展, 2026, 16(3): 706-718.

Mengjie DONG, Peiwen FAN, Ruozheng WANG. Transcriptomic Analysis of the Role of NFIA in HER2-positive Breast Cancer Brain Metastasis[J]. Current Biotechnology, 2026, 16(3): 706-718.

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链接本文: https://swjsjz.magtechjournal.com/CN/10.19586/j.2095-2341.2026.0016

https://swjsjz.magtechjournal.com/CN/Y2026/V16/I3/706

图/表 7

表1 2例单细胞测序的乳腺癌脑转移患者的临床病理特征

Table 1 Clinicopathological characteristics of two patients with brain metastasis from breast cancer by single cell sequencing

病人ID	性别	年龄	月经状态	转移部位	转移类型	既往治疗
BCBM-1	女性	47	绝经前	脑	异时性转移	化疗
BCBM-2	女性	45	绝经前	脑	异时性转移	化疗

表2 27例免疫组化患者的临床病理特征

Table 2 Clinical and pathological characteristics of 27 immunohistochemistry patients

变量	特征	总体（n=27)	百分比/%
肿瘤部位	原发乳腺癌	12	30.8
	乳腺癌脑转移	27	100.0
临床分期	临床分期Ⅰ	2	7.4
	临床分期Ⅱ	8	29.6
	临床分期Ⅲ	12	44.4
	临床分期Ⅳ	5	18.6
年龄（岁）		47（40~66）
月经状态	绝经前	19	70.3
	绝经后	8	29.7
分子分型	Luminal型	13	48.1
	HER2阳性型	11	40.7
	TNBC	3	11.2
组织学类型	浸润性导管癌	27	100.0
	其他	0
转移模式	异时性脑转移	27	100.0
既往系统治疗	药物治疗	20	74.1
	放疗	22	81.5

图1 NFIA在HER2阳性乳腺癌脑转移中的表达水平及与预后的关系A：NFIA在多种肿瘤组织中的表达水平；B：NFIA在原发乳腺癌组织与正常乳腺组织中的表达比较；C：基于KM Plotter数据库的Kaplan-Meier生存分析；D：基于TCGAHER2阳性乳腺癌癌患者多因素COX分析的森林图；E：基于GEO数据集验证NFIA在乳腺癌原发灶及乳腺癌脑转移灶中的表达差异；F：NFIA在乳腺癌脑转移不同分子分型中的表达分布情况；G：NFIA在HER2阳性原发乳腺癌和乳腺癌脑转移中的表达情况；H：HER2阳性乳腺癌脑转移患者中NFIA高表达组与低表达组的Kaplan-Meier总体生存曲线分析。*、**、***表示差异在P0.05、P0.01、P0.001水平上具有统计学意义。

Fig. 1 Expression of NFIA in HER2-positive breast cancer brain metastasis and its correlation with prognosis

图2 免疫组织化学验证NFIA在HER2阳性BCBM中的表达水平及与预后的关系A：免疫组化配对样本中NFIA在BC与BCBM组织之间的表达差异；B：原发乳腺癌及其脑转移灶中NFIA的蛋白表达水平；C：免疫组化样本中NFIA在BCBM不同分子分型中的表达差异；D：BCBM不同分子分型中NFIA的蛋白表达水平；E：免疫组化样本中HER2阳性BCBM患者按NFIA表达水平分组的Kaplan-Meier总体生存（overall survival，OS）曲线；F：HER2阳性BCBM灶中NFIA高表达组与低表达组之间的蛋白表达差异。*、**、****表示差异在P0.05、P0.01、P0.000 1水平具有统计学意义。

Fig. 2 Immunohistochemical validation of NFIA expression in HER2-positive BCBM and its correlation with prognosis

图3 NFIA对高恶性特征肿瘤的标记作用A：来源于HER2阳性BCBM的18 307个高质量单细胞的聚类结果，不同颜色表示不同细胞簇；B：各主要细胞类型的特异性高表达标记基因，颜色表示基因的平均表达水平；C：HER2阳性BCBM中18 307个单细胞的细胞类型注释结果，不同颜色代表不同细胞类型；D：HER2阳性BCBM中各细胞类型的组成比例；E：NFIA在HER2阳性BCBM不同细胞类型中的表达分布；F：HER2阳性BCBM上皮细胞的再聚类结果，不同颜色代表不同上皮细胞亚群；G：HER2阳性BCBM上皮细胞中NFIA高表达组与低表达组的拷贝数变异谱；H：HER2阳性BCBM上皮细胞中NFIA高表达组与低表达组的CNV评分差异。****表示差异在P0.000 1水平上具有统计学意义。

Fig. 3 The marker effect of NFIA in highly malignant tumors

图4 NFIA表达水平与肿瘤细胞功能的关系A：NFIA高表达组与低表达组中显著差异富集的前10条通路，绿色表示NFIA高表达组富集的通路，蓝色表示NFIA低表达组富集的通路；B：上皮-间质转化信号通路在NFIA高、低表达组的基因集富集分析结果；C：NFIA高表达组与低表达组在细胞发育轨迹中的分布差异；D：EMT分数在细胞发育轨迹中的变化；E：拟时序分析的分支热图；F：NFIA调节子AUC随时间的变化；G：NFIA调节子AUC与EMT的关系；H：NFIA调节子AUC高表达组的高表达转录因子

Fig. 4 Correlation of NFIA expression levels with the functional states of tumor cells

图5 NFIA的表达水平对TME的影响A：HER2阳性BCBM样本中主要细胞类型之间的配体-受体相互作用数量，连线颜色表示信号传递方向，线条粗细表示相互作用数量；B：HER2阳性BCBM样本中主要细胞类型之间的配体-受体相互作用强度，连线颜色表示信号传递方向，线条粗细表示相互作用强度；C：HER2阳性BCBM样本中主要细胞类型之间的相互作用强度和作用数量；D：NFIA高表达组与低表达组与其他细胞类型之间相互作用的数量及强度差异；E：NFIA高表达组与低表达组作为信号发送者、其他细胞类型作为信号接收者时的配体-受体相互作用差异；F：其他细胞类型作为信号发送者、NFIA高表达组与低表达组作为信号接收者时的配体-受体相互作用差异

Fig. 5 The effects of NFIA expression level on TME

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转录组学解析NFIA在HER2阳性乳腺癌脑转移中的作用研究

Transcriptomic Analysis of the Role of NFIA in HER2-positive Breast Cancer Brain Metastasis

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