河北医科大学学报 ›› 2022, Vol. 43 ›› Issue (5): 564-569.doi: 10.3969/j.issn.1007-3205.2022.05.013

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宫颈癌中影响预后的生物分子及免疫细胞浸润

  

  1. 1.延安大学附属医院放疗科,陕西 延安 716000;2.延安大学医学院,陕西 延安 716000
  • 出版日期:2022-05-25 发布日期:2022-05-30
  • 作者简介:苏亚妮(1995-),女,陕西山阳人,延安大学附属医院医师,医学硕士,从事肿瘤放射敏感性及免疫微环境研究。
  • 基金资助:

    国家自然科学基金项目(82060452);陕西省教育厅科研计划项目(18JK0864)

Biomolecules and immune cell infiltration affecting the prognosis of cervical cancer

  1. 1.Department of Oncology Radiotherapy, the Affiliated Hospital of Yanan University, Shaanxi Province, Yan′an 716000, China; 2.Yan′an University School of Medicine, Shaanxi Province, Yan′an 716000, China

  • Online:2022-05-25 Published:2022-05-30

摘要:

目的  探讨预测宫颈癌预后的潜在生物标志物和免疫浸润细胞,为宫颈癌治疗和预后研究提供理论依据和研究方向。

方法  基因表达综合数据库下载宫颈癌组织的芯片数据集(GSE9750),R的“limma”包鉴定差异表达基因,使用R的“clusterProfiler”包进行基因本体论和京都基因与基因组百科全书富集分析。用STRING构建蛋白-蛋白互作网络。利用基因表达谱交互式分析平台验证宫颈癌肿瘤组织和正常样品中抑制素βA(inhibin beta AINHBA)的表达水平并预测预后。在R中经“e1071”、“parallel”和“preprocessCore”包用“CIBERSORT”软件获得宫颈癌组织样本的免疫浸润细胞表达情况。

结果  最终鉴定出与宫颈癌预后高度相关的关键基因INHBA,宫颈癌组织中INHBA的表达水平明显升高,高表达组INHBA的生存周期明显短于低表达组。与正常宫颈组织样本相比,宫颈癌样本中初始CD4+ T细胞、未活化的自然杀伤细胞、M0M1巨噬细胞均升高;而未活化的CD4+记忆性T细胞、单核细胞、未活化的树突状细胞在宫颈癌样本中表达明显降低。未活化的CD4+记忆性T细胞和未活化的树突状细胞呈正相关,未活化的树突状细胞和浆细胞呈负相关。

结论  与宫颈癌预后高度相关的基因INHBA高表达。在宫颈癌中的免疫浸润细胞,初始CD4+ T细胞、未活化的自然杀伤细胞、M0M1巨噬细胞上调,未活化的CD4+记忆性T细胞、单核细胞和未活化的树突状细胞下调。未活化的CD4+记忆性T细胞和未活化的树突状细胞呈正相关,未活化的树突状细胞和浆细胞呈负相关。为宫颈癌的治疗和预后研究提供了新的依据。

关键词: 宫颈肿瘤, 预后;抑制素β亚单位

Abstract:

Objective  To study the potential biomarkers and immune cell infiltration that can predict the prognosis of cervical cancer, and to provide theoretical basis and research direction for the research of cervical cancer treatment and prognosis.

Methods  The microarray dataset(GSE9750) of cervical cancer tissue was downloaded from Gene Expression Omnibus(GEO), and the “limma” package of R was used to identify differentially expressed genes(DEGs). The “clusterProfiler”package of R was used for gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) enrichment analyses. STRING was used to construct a protein-protein interaction network(PPI). The gene expression profiling interactive analysis(GEPIA) platform was used to verify the expression level of inhibin beta A(INHBA) in cervical cancer tissues and normal samples and predict the prognosis. The “CIBERSORT” software was used to obtain the expression of immune infiltrating cells in cervical cancer tissue samples through the three packages e1071”, “parallel” and “preprocess Core” of R.

Results  Ultimately, the key gene INHBA, which was highly correlated with the prognosis of cervical cancer, was identified. The expression level of INHBA in cervical cancer tissues was significantly increased, and the life cycle of the high expression INHBA was significantly shorter than that of the low expression group. Compared with normal cervical tissue samples, native CD4+ T cells, unactivated natural killer(NK) cells, and M0 and M1 macrophages were all elevated in cervical cancer samples, while unactivated memory CD4+ T cells, monocytes, and unactivated dendritic cells were significantly reduced in cervical cancer samples.Unactivated dendritic cells were positively correlated with unactivated CD4+ T cells and negatively correlated with plasma cells.

Conclusion  In this study, the highly expressed gene INHBA, which is highly correlated with the prognosis of cervical cancer, is obtained. Immune infiltrating cells in cervical cancer, native CD4+ T cells, unactivated NK cells, M0 and M1 macrophages are upregulated, while unactivated memory CD4+ T cells, monocytes, and unactivated dendritic cells are downregulated. In addition, unactivated dendritic cells are positively correlated with unactivated memory T cells, and negatively correlated with plasma cells. The results of this study provide a new basis for the treatment and prognosis of cervical cancer.

Key words: uterine cervical neoplasms, prognosis;  inhibin-beta subunits