NCAPH在肺鳞癌中表达的临床意义及与免疫微环境浸润的关系

doi:10.3877/cma.j.issn.1674-0785.2023.04.014

目的

分析非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H（NCAPH）在肺鳞癌（LUSC）中的表达及其与临床特征、预后、免疫细浸润的关系，并预测其生物学功能。

方法

根据癌症基因组图谱（TCGA）数据库中LUSC基因表达数据及临床信息，分析NCAPH在肿瘤组织和正常组织中的表达差异，分析NCAPH表达与LUSC临床特征的关系；并通过Kaplan-Meier法和COX回归分析NCAPH表达与LUSC患者预后的关系。通过GSEA富集分析预测NCAPH在LUSC中可能参与的信号通路。采用CIBERSORT反卷积算法分析NCAPH表达与免疫浸润的关系。

结果

NCAPH在LUSC肿瘤组织中高表达（P＜0.05），且与年龄、性别、临床分期、肿瘤大小、淋巴结转移及远处转移相关；生存分析表明NCAPH高表达组患者比低表达组患者预后差（P＜0.05），且NCAPH表达是LUSC的独立预后因素（HR=0.522，95%CI：0.358~0.762，P＜0.001）。富集分析结果表明NCAPH主要富集一系列生物学相关的过程，如细胞周期、DNA复制等。免疫浸润分析结果显示，LUSC肿瘤组织中NCAPH的高表达与幼稚B细胞、M1样巨噬细胞、活化NK细胞、滤泡辅助性T细胞的浸润成正相关（P＜0.05），与记忆B细胞、活化树突状细胞、静息NK细胞及活化记忆CD4⁺T细胞的浸润成负相关（P＜0.05）。

结论

NCAPH在LUSC中呈高表达状态，其高表达与LUSC患者的不良预后相关，且其表达水平与免疫浸润具有相关性。NCAPH有望成为LUSC诊断和预后相关的新标志物。

关键词: 肺鳞癌, NCAPH, 预后, 免疫浸润, 富集分析

Objective

To detect the expression of non-SMC condensin I complex subunit H (NCAPH) in lung squamous cell carcinoma (LUSC), to explore its relationship with clinical features, prognosis, and immune fine infiltration, and to predict its biological function.

Methods

NCAPH expression differences in tumor tissues and normal tissues, and the association between NCAPH expression and LUSC clinical characteristics were examined based on the LUSC gene expression data and clinical information in the Cancer Genome Atlas (TCGA) database. By using the Kaplan-Meier technique and COX regression, the association between NCAPH expression and the prognosis of LUSC patients was analyzed. Gene set enrichment analysis (GSEA) was used to identifty the potential signaling pathways involving NCAPH in LUSC. The CIBERSORT deconvolution technique was used to examine the association between NCAPH expression and immune cell infiltration.

Results

NCAPH expression was significantly upregulated in LUSC (P＜0.05), and it was correlated with age, gender, stage, tumor size, lymph node metastasis, and distant metastasis. Survival analysis revealed that patients with high NCAPH expression had a worse prognosis than those with low expression (P＜0.05), and NCAPH expression was an independent risk factor for the prognosis of LUSC (hazard ratio=0.522, 95% confidence interval (CI): 0.358-0.762, P＜0.001). GSEA enrichment analysis showed that NCAPH was mainly enriched a series of biologically related processes, such as cell cycle and DNA replication. Immuno-infiltration analysis showed that high expression of NCAPH in LUSC tumor tissues was positively correlated with the levels of naive B cells, M1 macrophages, activated NK cells, and follicular helper T cells (P＜0.05), and negatively correlated with the levels of memory B cells, activated dendritic cells, dormant NK cells, and activated CD4+ memory T cells (P＜0.05).

Conclusion

NCAPH is highly expressed in LUSC, and its high expression is associated with both immune infiltration and the poor prognosis of LUSC patients. NCAPH is anticipated to emerge as a potential diagnostic and prognostic marker for LUSC.

Key words: Lung squamous cell carcinoma, NCAPH, Prognosis, Immune infiltration, Gene set enrichment analysis

图1 NCAPH在肿瘤组织与正常组织中的差异表达。图a为NCAPH在不同肿瘤组织和正常组织中的表达；图b为NCAPH表达在LUSC肿瘤组织与正常组织中的差异；图c为NCAPH表达在LUSC配对肿瘤组织与正常组织中的差异；图d为NCAPH诊断LUSC的ROC曲线注：NCAPH为非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H；LUSC为肺鳞癌

图2 NCAPH表达与LUSC临床特征的相关性。图a为年龄；图b为性别；图c为临床分期；图d为肿瘤大小；图e为淋巴结有无转移；图f为有无远处转移注：NCAPH为非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H；LUSC为肺鳞癌

图3 NCAPH表达与LUSC患者预后的关系。图a为NCAPH高、低表达组生存曲线；图b为NCAPH多因素COX回归分析注：NCAPH为非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H；LUSC为肺鳞癌

表1 影响肺鳞癌患者预后的单因素及多因素Cox回归分析

临床特征	单因素		多因素
临床特征	HR（95%CI）	P值	HR（95%CI）	P值
年龄	0.727（0.528~1.000）	0.050	0.713（0.518~0.982）	0.038
性别	1.360（0.944~1.958）	0.099	1.302（0.902~1.880）	0.159
TNM分期	1.392（0.974-1.989）	0.070
T分期	1.412（0.973~2.048）	0.069	1.514（1.039~2.206）	0.031
N分期	1.062（0.780~1.444）	0.704
M分期	2.432（0.898~6.591）	0.080	2.423（0.887~6.617）	0.084
NCAPH	0.545（0.375~0.791）	0.001	0.522（0.358~0.762）	＜0.001

表1 影响肺鳞癌患者预后的单因素及多因素Cox回归分析

临床特征	单因素		多因素
临床特征	HR（95%CI）	P值	HR（95%CI）	P值
年龄	0.727（0.528~1.000）	0.050	0.713（0.518~0.982）	0.038
性别	1.360（0.944~1.958）	0.099	1.302（0.902~1.880）	0.159
TNM分期	1.392（0.974-1.989）	0.070
T分期	1.412（0.973~2.048）	0.069	1.514（1.039~2.206）	0.031
N分期	1.062（0.780~1.444）	0.704
M分期	2.432（0.898~6.591）	0.080	2.423（0.887~6.617）	0.084
NCAPH	0.545（0.375~0.791）	0.001	0.522（0.358~0.762）	＜0.001

图4 NCAPH基因GSEA富集结果注：NCAPH为非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H；GSEA为基因富集分析

图5 LUSC患者中NCAPH高低表达组免疫浸润情况。图a为22种免疫细胞占比的柱状图；图b为各种免疫细胞构成比箱型图；图c为各种免疫细胞分布图；图d为每种免疫细胞占比相关性热图注：NCAPH为非染色体结构维持蛋白凝缩蛋白复合体Ⅰ亚单位H；LUSC为肺鳞癌

图6 NCAPH表达与免疫细胞的相关性

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NCAPH expression in lung squamous cell carcinoma: clinical significance and relationship with immune microenvironment infiltration

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NCAPH expression in lung squamous cell carcinoma: clinical significance and relationship with immune microenvironment infiltration