Screening of target genes for metastatic prostate cancer based on single cell sequencing
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摘要: 目的:基于单细胞测序探寻转移性前列腺癌潜在靶基因。方法:由GEO数据库下载转移性前列腺癌患者循环肿瘤细胞(CTCs)单细胞测序数据,使用R 3.6.2软件进行PCA主成分分析及tSNE(T分布随机近邻嵌入)聚类分析筛选核心基因并通过人蛋白质图谱在线数据库进行验证。基于estimate及cibersort包将上述核心基因进行22种免疫细胞浸润分析及免疫微环境分析。结果:由GEO数据库下载GSE67980数据集中共18例有骨转移的转移性前列腺癌患者164个CTCs纳入研究。通过PCA(主成分分析)及tSNE聚类分析确定HBB(β珠蛋白)为潜在靶基因。免疫组织化学染色提示相比于正常前列腺组织与低级别前列腺肿瘤组织,高级别前列腺组织中HBB蛋白显著高表达。免疫细胞浸润及免疫微环境分析提示HBB高表达与肿瘤微环境中基质细胞及免疫细胞含量成正比且与M2巨噬细胞及肥大细胞浸润正相关,与M1巨噬细胞浸润负相关。结论:HBB可作为转移性前列腺癌潜在的靶基因,并为转移性前列腺癌的研究提供了新的方向。Abstract: Objective: To explore the potential target genes of metastatic prostate cancer based on single cell sequencing.Methods: The single cell sequencing data of circulating tumor cells(CTCs) of patients with metastatic prostate cancer was downloaded from GEO database. Core genes were screened by PCA and tSNE using R 3.6.2 software and verified by human protein atlas online database. Based on estimate and cibersort packages, the above core genes were analyzed by immune cell infiltration and immune microenvironment analysis.Results: One hundred and sixty-four CTCs of 18 patients with metastatic prostate cancer with bone metastasis were included in the study by downloading GSE67980 dataset from GEO database. HBB was identified as a potential target gene by PCA and tSNE analysis. Immunohistochemical staining showed that the expression of HBB protein in high-grade prostate tissue was significantly higher than that in normal prostate tissue and low-grade prostate tumor tissue. The analysis of immune cell infiltration and immune microenvironment showed that the high expression of HBB was proportional to the content of stromal cells and immune cells in tumor microenvironment, positively correlated with M2 macrophage and mast cell infiltration, and negatively correlated with M1 macrophage infiltration.Conclusion: HBB can be used as a potential diagnostic marker and provides a new research direction for the treatment of metastatic prostate cancer.
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[1] Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[2] Culp MB,Soerjomataram I,Efstathiou JA,et al.Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates[J].Eur Urol,2020,77(1):38-52.
[3] 谭祎,刘艳,宋羽葳,等.循环肿瘤细胞与转移性前列腺癌患者预后关系的Meta分析[J].肿瘤防治研究,2016,43(9):783-788.
[4] Van Loo P,Voet T.Single cell analysis of cancer genomes[J].Curr Opin Genet Dev,2014,24:82-91.
[5] Apostolidis SA,Stifano G,Tabib T,et al.Single Cell RNA Sequencing Identifies HSPG2 and APLNR as Markers of Endothelial Cell Injury in Systemic Sclerosis Skin[J].Front Immunol,2018,9:2191.
[6] 蒙杰,卢奕,张健.肿瘤微环境与前列腺癌骨转移研究进展[J].肿瘤防治研究,2018,45(8):593-597.
[7] Kim J,Bae JS.Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment[J].Mediators Inflamm,2016,2016:6058147.
[8] Wang G,Zhao D,Spring DJ,et al.Genetics and biology of prostate cancer[J].Genes Dev,2018,32(17-18):1105-1140.
[9] Body JJ,Casimiro S,Costa L.Targeting bone metastases in prostate cancer:improving clinical outcome[J].Nat Rev Urol,2015,12(6):340-356.
[10] Aceto N,Toner M,Maheswaran S,et al.En Route to Metastasis:Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition[J].Trends Cancer,2015,1(1):44-52.
[11] Onda M,Akaishi J,Asaka S,et al.Decreased expression of haemoglobin beta(HBB)gene in anaplastic thyroid cancer and recovery of its expression inhibits cell growth[J].Br J Cancer,2005,92(12):2216-2224.
[12] Ponzetti M,Capulli M,Angelucci A,et al.Non-conventional role of haemoglobin beta in breast malignancy[J].Br J Cancer,2017,117(7):994-1006.
[13] Zheng Y,Miyamoto DT,Wittner BS,et al.Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination[J].Nat Commun,2017,8:14344.
[14] Li X,Wu Z,Wang Y,et al.Characterization of adult α-and β-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults[J].PLoS One,2013,8(1):e54342.
[15] Nenu I,Gafencu GA,Popescu T,et al.Lactate-A new frontier in the immunology and therapy of prostate cancer[J].J Cancer Res Ther,2017,13(3):406-411.
[16] 张子明,柴国静,宋淑霞.肿瘤相关巨噬细胞的极化及其对肿瘤治疗的影响[J].中国免疫学杂志,2019,35(8):1018-1023.
[17] 许召良,马志方,岳亮,等.肥大细胞对前列腺癌细胞上皮间质转化的作用[J].中国药物与临床,2015,15(9):1225-1228.
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