PFDN5 在乳腺癌中扮演双重角色并调控肿瘤免疫微环境综合生物信息学分析和实验验证的启示

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-10-11 DOI:10.1016/j.gene.2024.149000
Ping Wen , Dongping Jiang , Fanli Qu , Guanwen Wang , Ningning Zhang , Qing Shao , Yuxin Huang , Sisi Li , Long Wang , Xiaohua Zeng
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引用次数: 0

摘要

背景虽然乳腺癌患者的预后有所改善,但乳腺癌仍是全球妇女的主要死因。预折叠蛋白 5(PFDN5)作为预折叠蛋白复合物的一个亚基,在帮助新合成的蛋白质正确折叠方面起着至关重要的作用。我们进行了生物信息学分析,研究 PFDN5 与乳腺癌患者生存期以及各种临床病理特征之间的相关性。此外,我们还采用了多种检测方法来验证 PFDN5 在乳腺癌中的生物学功能。结果与正常组织相比,PFDN5在乳腺癌组织中的表达水平较低,而PFDN5的低表达与较差的预后相关。PFDN5 导致细胞周期 G2/M 期停滞,并降低了乳腺癌细胞的增殖潜力。然而,PFDN5 还能促进乳腺癌细胞的迁移和侵袭。此外,RNA-seq分析显示,PFDN5参与了细胞周期和TGF-β信号通路。此外,PFDN5 通过促进巨噬细胞向 M1 表型极化,对肿瘤免疫微环境有显著影响,并与 CD8+ T 细胞浸润水平呈正相关。因此,PFDN5有望成为预测乳腺癌转移和预后的重要生物标记物。
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PFDN5 plays a dual role in breast cancer and regulates tumor immune microenvironment: Insights from integrated bioinformatics analysis and experimental validation

Background

Although the prognosis for patients with breast cancer has improved, breast cancer remains the leading cause of death for women worldwide. Prefoldin 5 (PFDN5), as a subunit of the prefoldin complex, plays a vital role in aiding the correct folding of newly synthesized proteins. However, the exact impact of PFDN5 on breast cancer development and its prognostic implications remain unclear.

Methods

We conducted bioinformatics analysis to investigate the correlation between PFDN5 and patient survival, as well as various clinicopathological characteristics in breast cancer. Additionally, various assays were employed to validate the biological functions of PFDN5 in breast cancer. Finally, RNA sequencing (RNA-seq) was utilized to investigate the molecular mechanisms associated with PFDN5.

Results

Compared to normal tissues, PFDN5 exhibited lower expression levels in breast cancer tissues, and lower expression of PFDN5 is associated with poorer prognosis. PFDN5 led to G2/M phase arrest in the cell cycle and reduced proliferative potential in breast cancer cells. However, PFDN5 also promoted migration and invasion of breast cancer cells. Also, RNA-seq analysis revealed an involvement of PFDN5 in the cell cycle and TGF-β signaling pathway. Furthermore, PFDN5 had a significant impact on tumor immune microenvironment by promoting macrophage polarization towards the M1 phenotype and exhibited a positive correlation with CD8+ T cell infiltration levels.

Conclusions

PFDN5 plays a dual role in breast cancer and serves as a key factor in tumor immune microenvironment. Therefore, PFDN5 holds promise as a valuable biomarker for predicting both metastatic and prognosis in breast cancer.
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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