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热休克蛋白家族A(Hsp70)成员14(HSPA14)在乳腺癌中的作用:对肿瘤发生、免疫反应调节及个性化治疗的影响

The role of HSPA14 in breast cancer: implications for tumorigenesis, immune response modulation, and personalized therapies.

作者信息

Zhao Ruipeng, Zhu Xiaocun, Wei Wan, Zhen Linlin

机构信息

Department of Thyroid and Breast Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.

出版信息

Int J Hyperthermia. 2025 Dec;42(1):2452922. doi: 10.1080/02656736.2025.2452922. Epub 2025 Jan 19.

DOI:10.1080/02656736.2025.2452922
PMID:39828281
Abstract

BACKGROUND

Heat shock proteins have been implicated in the process of carcinogenesis. HSPA14, a member of the heat shock protein family, remains poorly understood in terms of its significance and pathomechanisms in breast cancer.

METHODS

We analyzed the expression levels of HSPA14 and its prognostic significance in breast cancer using TCGA data. TCGA data was used to investigate the association between HSPA14 expression and clinicopathological features in breast cancer patients. GSEA analysis was conducted to identify the biological function of HSPA14. Spearman's correlation analysis was performed to examine the correlation between HSPA14 expression and immune cell infiltration, as well as immune checkpoint genes. Single cell transcriptomic data from GSE114727 was utilized to calculate the expression of HSPA14 in different cell subpopulations. The data on HSPA14 levels and drug sensitivity were extracted from the CellMiner dataset. The mRNA expression of HSPA14 was validated through cell experiments.

RESULTS

HSPA14 expression is elevated in breast cancer, which is associated with poor overall survival. It can serve as a diagnostic biomarker for breast cancer patients. Pathway analysis revealed that HSPA14-associated differential genes are involved in cell cycle, apoptosis, cellular response to heat stress, and more. Additionally, HSPA14 expression is significantly correlated with the immune microenvironment. The expression of HSPA14 may also indicate drug sensitivity.

CONCLUSION

Our study elucidates the involvement of HSPA14 in tumorigenesis, particularly in modulating the immune response, shaping the immune microenvironment, and contributing to drug resistance, which are pivotal for the development of personalized breast cancer therapies.

摘要

背景

热休克蛋白与致癌过程有关。热休克蛋白家族成员HSPA14在乳腺癌中的意义和发病机制仍知之甚少。

方法

我们使用TCGA数据分析了HSPA14在乳腺癌中的表达水平及其预后意义。利用TCGA数据研究HSPA14表达与乳腺癌患者临床病理特征之间的关联。进行基因集富集分析(GSEA)以确定HSPA14的生物学功能。进行Spearman相关性分析以检验HSPA14表达与免疫细胞浸润以及免疫检查点基因之间的相关性。利用来自GSE114727的单细胞转录组数据计算HSPA14在不同细胞亚群中的表达。从CellMiner数据集中提取HSPA14水平和药物敏感性的数据。通过细胞实验验证HSPA14的mRNA表达。

结果

HSPA14在乳腺癌中表达升高,这与总体生存率低有关。它可作为乳腺癌患者的诊断生物标志物。通路分析显示,与HSPA14相关的差异基因参与细胞周期、凋亡、细胞对热应激的反应等。此外,HSPA14表达与免疫微环境显著相关。HSPA14的表达也可能表明药物敏感性。

结论

我们的研究阐明了HSPA14参与肿瘤发生,特别是在调节免疫反应、塑造免疫微环境和导致耐药性方面,这些对于个性化乳腺癌治疗的发展至关重要。

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