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子宫内膜癌中精子相关抗原 5 表达上调与预后不良和免疫失调有关,并促进细胞迁移和侵袭。

Upregulation of sperm-associated antigen 5 expression in endometrial carcinoma was associated with poor prognosis and immune dysregulation, and promoted cell migration and invasion.

机构信息

Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Department of BigData, Beijing Medintell Bioinformatic Technology Co., LTD, Beijing, China.

出版信息

Sci Rep. 2024 Jun 11;14(1):13415. doi: 10.1038/s41598-024-64354-4.


DOI:10.1038/s41598-024-64354-4
PMID:38862557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11166665/
Abstract

Sperm-associated antigen 5 (SPAG5) regulates cancer cell invasion and is involved in the progression of many cancers. However, the role of SPAG5 in endometrial carcinoma (EC) is still unknown. The purpose of this study was to explore the role of SPAG5 in EC and its potential molecular mechanism. The UALCAN tool and cBioPortal were used to analyze the expression and alterations of SPAG5 in EC, respectively. OncoLnc was used for survival analysis. We analyzed the effects of SPAG5 on immune cell infiltration and the expression levels of immune checkpoints. We also overexpressed and knocked down SPAG5 in EC cells to explore the effect of SPAG5 regulation on migration, invasion, apoptosis, and the cell cycle of EC cells. We found that SPAG5 was overexpressed and the SPAG5 gene was often mutated in EC. High SPAG5 expression was significantly associated with poor overall survival in patients with EC. SPAG5 also affected the level of immune cell infiltration in the TIME and the expression of immune checkpoints lymphocyte activating 3 (LAG3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with EC. It may also be involved in the immunotherapy response in these patients. In vitro experiments showed that SPAG5 promotes cancer cell migration and invasion. In conclusion, this study lays the foundation for further understanding the molecular mechanisms of EC involving SPAG5 and contributes to diagnosing and managing this disease.

摘要

精子相关抗原 5(SPAG5)调节癌细胞侵袭,参与多种癌症的进展。然而,SPAG5 在子宫内膜癌(EC)中的作用尚不清楚。本研究旨在探讨 SPAG5 在 EC 中的作用及其潜在的分子机制。分别使用 UALCAN 工具和 cBioPortal 分析了 SPAG5 在 EC 中的表达和改变。OncoLnc 用于生存分析。我们分析了 SPAG5 对免疫细胞浸润和免疫检查点表达水平的影响。我们还在 EC 细胞中过表达和敲低 SPAG5,以探讨 SPAG5 调节对 EC 细胞迁移、侵袭、凋亡和细胞周期的影响。我们发现 SPAG5 在 EC 中过表达,并且 SPAG5 基因经常发生突变。SPAG5 高表达与 EC 患者总生存期不良显著相关。SPAG5 还影响了 TIME 中免疫细胞浸润的水平和 EC 患者中淋巴细胞激活 3(LAG3)和 T 细胞免疫受体具有免疫球蛋白和 ITIM 结构域(TIGIT)的免疫检查点的表达。它可能也参与了这些患者的免疫治疗反应。体外实验表明,SPAG5 促进了癌细胞的迁移和侵袭。综上所述,本研究为进一步了解涉及 SPAG5 的 EC 的分子机制奠定了基础,并有助于诊断和管理这种疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/172e04a7731a/41598_2024_64354_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/257be09e8ae8/41598_2024_64354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/0f896f277b47/41598_2024_64354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/086d539ca061/41598_2024_64354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/a61fc902b96a/41598_2024_64354_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/9af99a758672/41598_2024_64354_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/9a1a3b34ecd7/41598_2024_64354_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/172e04a7731a/41598_2024_64354_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/257be09e8ae8/41598_2024_64354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/0f896f277b47/41598_2024_64354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/086d539ca061/41598_2024_64354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/a61fc902b96a/41598_2024_64354_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/9af99a758672/41598_2024_64354_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/9a1a3b34ecd7/41598_2024_64354_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dfa/11166665/172e04a7731a/41598_2024_64354_Fig7_HTML.jpg

相似文献

[1]
Upregulation of sperm-associated antigen 5 expression in endometrial carcinoma was associated with poor prognosis and immune dysregulation, and promoted cell migration and invasion.

Sci Rep. 2024-6-11

[2]
SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation.

J Exp Clin Cancer Res. 2018-9-18

[3]
SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway.

Cell Death Dis. 2014-5-22

[4]
SPAG5 upregulation contributes to enhanced c-MYC transcriptional activity via interaction with c-MYC binding protein in triple-negative breast cancer.

J Hematol Oncol. 2019-2-8

[5]
SPAG5 contributes to the progression of gastric cancer by upregulation of Survivin depend on activating the wnt/β-catenin pathway.

Exp Cell Res. 2019-3-21

[6]
Sperm-Associated Antigen 5 Expression Is Increased in Hepatocellular Carcinoma and Indicates Poor Prognosis.

Med Sci Monit. 2018-8-29

[7]
MiR-29a-5p inhibits proliferation and invasion and induces apoptosis in endometrial carcinoma via targeting TPX2.

Cell Cycle. 2018-7-23

[8]
Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression-based study.

J Gene Med. 2020-4

[9]
SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma.

Mol Cancer. 2018-8-8

[10]
SPAG5 promotes the proliferation, migration, invasion, and epithelial-mesenchymal transformation of colorectal cancer cells by activating the PI3K/AKT signaling pathway.

Chin J Physiol. 2023

本文引用的文献

[1]
Bioinformatic Analysis of m6A Regulator-Mediated RNA Methylation Modification Patterns and Immune Microenvironment Characterization in Endometriosis.

Biochem Genet. 2025-2

[2]
Selection of suitable internal control gene for assaying gene expression in rice through qRT-PCR during sheath blight infection.

J Biotechnol. 2023-1-20

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Nucleic Acids Res. 2023-1-6

[4]
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Nucleic Acids Res. 2023-1-6

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The splicing factor SF3B4 drives proliferation and invasion in cervical cancer by regulating SPAG5.

Cell Death Discov. 2022-7-19

[6]
Analysis of the immune checkpoint lymphocyte activation gene-3 (LAG-3) in endometrial cancer: An emerging target for immunotherapy.

Pathol Res Pract. 2022-8

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Ann Transl Med. 2022-1

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J Clin Lab Anal. 2022-4

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Int J Mol Sci. 2022-1-22

[10]
Identification of as an Immune-Associated Gene in Endometrial Carcinoma and Associated with Macrophage Infiltration by Bioinformatic Analysis.

J Healthc Eng. 2021

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