| 摘要: |
| 目的 探讨多发性内分泌肿瘤1型综合征（MEN1）的致病基因MEN1在乳腺癌中的表达及其临床意义。方法 利用肿瘤基因组图谱（TCGA）数据库分析乳腺癌患者MEN1表达水平与临床病理特征的关系，通过Kaplan-Meier生存分析法评估MEN1对乳腺癌预后的影响。采用基因本体（GO）、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）预测乳腺癌中MEN1相关和相互作用基因的功能和相关通路，利用单细胞测序数据库CancerSEA分析MEN1表达与肿瘤生物功能的相关性。采用肿瘤免疫估算资料（TIMER）数据库和单样本基因集富集分析（ssGSEA）研究乳腺癌中免疫细胞浸润水平与MEN1表达的相关性。结果 MEN1在乳腺癌患者中高表达，其表达水平与PAM50分型、围绝经期状态有关（均P＜0.05）。Kaplan-Meier生存分析结果显示，MEN1的高表达与较差的临床预后有关（P＝0.019）。GO和KEGG富集分析提示MEN1相关和相互作用基因参与组蛋白修饰、组蛋白-赖氨酸甲基化等生物学过程，甲基转移酶复合物、组蛋白甲基转移酶复合物等细胞组分，组蛋白-甲基转移酶活性等分子功能，肿瘤中的转录失调等功能通路。GSEA分析提示高表达MEN1表型涉及囊泡介导转运、补体级联反应、B细胞受体的信号转导、淋巴细胞与非淋巴细胞之间的相互作用、IL的信号转导、免疫系统中的细胞因子信号转导通路。CancerSEA单细胞测序数据分析显示，人乳腺癌细胞MDA-MB-231中MEN1的表达与血管生成呈正相关（P＜0.05）。TIMER分析显示，乳腺癌中MEN1表达与巨噬细胞、CD8+ T细胞的浸润水平呈负相关（均P＜0.05），与CD4+ T细胞的浸润水平呈正相关（P＜0.05）。ssGSEA分析结果提示18种免疫细胞的浸润水平与MEN1表达呈负相关（均P＜0.05）。结论 高水平的MEN1预示乳腺癌较短的总生存期，并可能与免疫细胞浸润相关。 |
| 关键词: 乳腺肿瘤 多发性内分泌肿瘤1型综合征基因 总生存期 免疫浸润 |
| DOI：10.16781/j.CN31-2187/R.20230287 |
| 投稿时间：2023-05-23修订日期：2023-12-13 |
| 基金项目:国家自然科学基金青年科学基金（81602617）. |
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| Association of MEN1 gene with prognosis and immune infiltration of breast cancer |
| SUN Xiaolu,HUANG Yandong,WANG Lianxiang,WU Daxi,HUANG Hejing* |
(Department of Ultrasound, The Second Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200003, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the expression and clinical significance of multiple endocrine neoplasia type 1 (MEN1) gene in breast cancer. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between MEN1 gene and clinicopathological characteristics of breast cancer. Kaplan-Meier method was used to observe the effect of MEN1 on survival of breast cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to predict the function and signaling pathways of MEN1 related and interacting genes. Tumor Immune Estimation Resource (TIMER) and single sample gene set enrichment analysis (ssGSEA) were used to investigate the correlation between the level of immune infiltration and MEN1 expression in breast cancer. Results MEN1 was highly expressed in breast cancer patients, and its expression level was related to PAM50 subtype and menopause status (both P＜0.05). Kaplan-Meier survival analysis showed that high MEN1 expression was associated with poor clinical outcome (P＝0.019). GO and KEGG enrichment analysis showed that MEN1 related and interacting genes were involved in biological processes (histone modification, histone-lysine methylation), cell components (methyltransferase complex and histone methyltransferase complex), molecular functions (histone-methyltransferase activity), and functional pathways (transcriptional disorders in tumors). GSEA identified that the highly expressed MEN1 phenotype was involved in vesicle-mediated transport, complement cascade, B-cell receptor signaling, lymphocyte-non-lymphocyte interaction, interleukin signaling, and cytokine signaling pathways in the immune system. CancerSEA single cell sequencing results indicated that the expression of MEN1 was positively correlated with angiogenesis in MDA-MB-231 cells (P＜0.05). TIMER analysis found that MEN1 in breast cancer was negatively correlated with the infiltration levels of macrophages and CD8+ T cells, and positively correlated with the infiltration level of CD4+ T cells (all P＜0.05). ssGSEA showed that the infiltration levels of 18 types of immune cells were negatively correlated with MEN1 expression (all P＜0.05). Conclusion High MEN1 level is associated with poor survival and immune infiltration in breast cancer patients. |
| Key words: breast neoplasms multiple endocrine neoplasia type 1 gene overall survival immune infiltration |
