| 李福平,代引海,杜志勇,等.生物信息学分析 FAM83D在乳腺癌中的表达及其临床意义[J].安徽医药,2025,29(8):1597-1602. |
| 生物信息学分析 FAM83D在乳腺癌中的表达及其临床意义 |
| Bioinformatics analysis of FAM83D expression and its clinical significance in breast cancer |
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| DOI：10.3969/j.issn.1009-6469.2025.08.022 |
| 中文关键词: 乳腺肿瘤 基因序列 纺锤体蛋白 序列相似性为 83的家族成员 D 生物信息学 预后标志物 免疫浸润 |
| 英文关键词: Breast neoplasms Genetic sequence Fusolin Prognostic biomarker Immune infiltration |
| 基金项目:陕西省科技厅重点研发计划项目( 2022SF-563) |
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| 中文摘要: |
| 目的利用生物信息学分析手段评估序列相似性为 83的家族成员 D(FAM83D)在乳腺癌中的表达及预后价值。方法收集 2022年 10月至 2023年 5月基因表达综合( GEO)、癌症基因组图谱( TCGA)、基因表达谱交互分析( GEPIA)2、人类蛋白谱(HPA)和肿瘤亚群基因表达和生存分析门户( UALCAN)等数据库中 FAM83D在乳腺癌中的表达数据及其与临床分期相关性数据，并分析 FAM83D的表达与分子分型和 TP53突变之间的相关性。此外，实时荧光定量 PCR进一步证实 FAM83D在乳腺癌细胞的表达情况。利用 Kaplan-Meier plotter数据库分析 FAM83D的表达对乳腺癌病人生存的影响，并对 FAM83D和其他相关病理参数进行单因素、多因素 Cox回归分析，构建列线图预后模型。利用功能富集分析门户( DAVID 6.8)对 FAM83D进行富集分析。通过肿瘤免疫评估综合数据库( TIMER 2.0)和肿瘤免疫系统交互数据库门户(TISIDB)分析了 FAM83D的表达与乳腺癌中免疫微环境具有一定的关联性。结果 FAM83D在乳腺癌组织和细胞中高表达， FAM83D的 mRNA水平在乳腺癌组织中表达水平( 3.11±0.64、4.43±1.45、3.10±1.24)明显高于正常乳腺组织( 3.09±0.24，1.64±0.81，0.83±0.61)各组比较均差异有统计学意义( P<0.05)并与乳腺癌病人肿瘤分期、分子分型和 TP53突变状态密切相关(均 P<0.05)。高表达的，FAM83D提示乳腺癌病人更短的总生存，期( OS)(HR=2.12，P<0.001)、无复发生存时间( RFS)(HR=2.11，P<0.001)、进展后生存时间( PPS)(HR=1.72，P=0.006)和无远处转移生存时间( DMFS)(HR=2.83，P<0.001)。 FAM83D、年龄、 M分期和绝经状态可作为乳腺癌病人的独立预后因素( HR=1.29，2.41，5.09，2.91；均 P<0.05)。基因本体( GO)和京都基因与基因组数据库( KEGG)富集分析结果显示， FAM83D不仅发挥着与微管、管蛋白结合的功能，还在细胞周期和 P53等相关信号通路显著富集。 FAM83D的表达与乳腺癌中 B细胞和辅助 T细胞 2等免疫细胞的浸润呈正相关，而与自然杀伤细胞和细胞样树突状细胞等免疫细胞的浸润呈负相关。此外， FAM83D的表达还与免疫刺激因子 PVR、ULBP1，免疫抑制因子 IDO1、LAG3和趋化因子 CCL7、CXCL10的表达呈正相关。结论 FAM83D在乳腺癌组织中高表达，与病人不良预后有关，可作为乳腺癌预后生物标志物。 |
| 英文摘要: |
| Objective To evaluate the expression and prognostic value of family with sequence similarity 83 member D (FAM83D) inbreast cancer using bioinformatics approaches.Methods We collect FAM83D expression data and its correlation with clinical stagingfrom databases including Gene Expression Synthesis (GEO), The Cancer Genome Map (TCGA), Gene Expression Profile InteractionAnalysis (GEPIA) 2, Human Protein Profile (HPA), and The University of ALabama at Birmingham CANcer data analysis Portal (UAL-CAN) from October 2022 to May 2023. The associations between FAM83D expression and molecular subtypes as well as TP53 muta-tion status were also analyzed. RT-qPCR validated FAM83D expression patterns in breast cancer cell lines. The Kaplan-Meier Plotter database assessed the impact of FAM83D expression on patient survival, followed by univariate and multivariate Cox regression analy-ses of FAM83D and related pathological parameters to establish a nomogram model. DAVID v6.8 was used for FAM83D enrichmentanalysis, while TIMER2.0 and TISIDB analyzed the correlation between FAM83D expression and the breast cancer immune microenvi.ronment.Results FAM83D was highly expressed in breast cancer tissues and cells, and the expression level of FAM83D mRNA inbreast cancer tissues (3.11±0.64, 4.43±1.45, 3.10±1.24) was significantly higher than that in normal breast tissues (3.09±0.24, 1.64±0.81, 0.83±0.61). There was a statistically significant difference between each group (P< 0.05), positively correlated with cancer stag-ing, molecular subtypes, and TP53 mutation (all P < 0.05). High FAM83D expression indicated shorter OS (HR=2.12, P < 0.001), RFS (HR=2.11, P <0.001), PPS (HR=1.72, P = 0.006), and DMFS (HR=2.83, P < 0.001). FAM83D, age, M stage, and menopausal status were independent prognostic factors (HR=1.29, 2.41, 5.09, 2.91; all P < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genesand Genomes (KEGG) enrichment analyses showed FAM83D was involved in microtubule/tubulin binding and enriched in cell cycleand p53 signaling pathways. FAM83D expression correlated positively with B cells and T helper type 2 (Th2) cell infiltration, and nega-tively with natural killer cells and plasmacytoid dendritic cell infiltration. It was also positively related to immunostimulatory molecules(PVR, ULBP1), immunoinhibitory molecules (IDO1, LAG3), and chemokines (CCL7, CXCL10).Conclusion FAM83D is highly ex-pressed in breast cancer tissues, associated with poor prognosis, and may serve as a prognostic biomarker. |
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