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原点识别复合物亚基 1(ORC1)是癌症的一个潜在的生物标志物和治疗靶点。

Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer.

机构信息

Integrated Chinese & Western Medicine Oncology Research Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.

College of life science, Gannan Normal University, Ganzhou, 341000, China.

出版信息

BMC Med Genomics. 2023 Oct 13;16(1):243. doi: 10.1186/s12920-023-01691-9.

Abstract

BACKGROUND

The origin recognition complex 1 (ORC1) is a large subunit of the origin recognition complex and acts as the master subunit of the precoding complex.

OBJECTIVE

To explore potential function and clinical significance of ORC1 in cancers.

METHODS

The expression level of ORC1 in different types of tumor tissues and matched normal tissues were detected by The Cancer Genome Atlas (TCGA) and validated by datasets from the gene expression omnibus (GEO) database. The association between ORC1 expression and infiltration levels of immune cell was analyzed. ORC1 and its co-expression genes were subjected to enrichment analysis to explore potential mechanisms in cancers, and the protein-protein interaction (PPI) network was constructed. Finally, the expression of ORC1 in tumor tissue and adjacent tissue was verified by immunohistochemistry (IHC).

RESULTS

ORC1 was highly expressed in the majority of tumors, and the expression level of ORC1 was associated with the pathological stages of ACC, LUAD, OV and SKCM. ORC1 was closely related with poor prognosis in ACC, LIHC, PAAD, READ and THCA. ORC1 in ACC and KICH was positively correlated with the infiltration level of immune cells while it was negatively correlated with the infiltration level of immune cells in THYM. Co-expression network analysis showed that CDCA3, GSG2, KIF2C, NCAPH and PLK1 were positively correlated with ORC1 in cancer, and enrichment analysis showed a correlation with cytosol, ATP binding and cell division. The expression of ORC1 in UCEC and KICH was higher than that in the adjacent tissues.

CONCLUSION

ORC1 over-expressed in most tumors and could be severed as a novel biomarker for diagnosis. This study revealed that ORC1 might inhibit tumor immunity and might be a potential therapeutic target in cancers.

摘要

背景

起始识别复合物 1(ORC1)是起始识别复合物的大亚基,作为预编码复合物的主亚基。

目的

探索 ORC1 在癌症中的潜在功能和临床意义。

方法

通过癌症基因组图谱(TCGA)检测不同类型肿瘤组织和配对正常组织中 ORC1 的表达水平,并通过基因表达综合数据库(GEO)数据集进行验证。分析 ORC1 表达与免疫细胞浸润水平的相关性。对 ORC1 及其共表达基因进行富集分析,以探讨癌症中的潜在机制,并构建蛋白质-蛋白质相互作用(PPI)网络。最后,通过免疫组织化学(IHC)验证肿瘤组织和相邻组织中 ORC1 的表达。

结果

ORC1 在大多数肿瘤中高表达,ORC1 的表达水平与 ACC、LUAD、OV 和 SKCM 的病理分期有关。ORC1 与 ACC、LIHC、PAAD、READ 和 THCA 的不良预后密切相关。在 ACC 和 KICH 中,ORC1 与免疫细胞浸润水平呈正相关,而在 THYM 中,ORC1 与免疫细胞浸润水平呈负相关。共表达网络分析显示,CDCA3、GSG2、KIF2C、NCAPH 和 PLK1 与癌症中 ORC1 呈正相关,富集分析显示与细胞质、ATP 结合和细胞分裂相关。UCEC 和 KICH 中 ORC1 的表达高于相邻组织。

结论

ORC1 在大多数肿瘤中高表达,可作为一种新的诊断标志物。本研究表明,ORC1 可能抑制肿瘤免疫,可能成为癌症的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/10571394/d4c4e5d9c2d9/12920_2023_1691_Fig2_HTML.jpg

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