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通过单细胞和机器学习鉴定癌症干细胞相关基因,用于预测前列腺癌预后和免疫治疗。

Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy.

机构信息

Cancer Research Centre Nantong, Affiliated Tumor Hospital of Nantong University, Nantong, China.

Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Immunol. 2024 Aug 29;15:1464698. doi: 10.3389/fimmu.2024.1464698. eCollection 2024.

Abstract

BACKGROUND

Cancer stem cells (CSCs) are a subset of cells within tumors that possess the unique ability to self-renew and give rise to diverse tumor cells. These cells are crucial in driving tumor metastasis, recurrence, and resistance to treatment. The objective of this study was to pinpoint the essential regulatory genes associated with CSCs in prostate adenocarcinoma (PRAD) and assess their potential significance in the diagnosis, prognosis, and immunotherapy of patients with PRAD.

METHOD

The study utilized single-cell analysis techniques to identify stem cell-related genes and evaluate their significance in relation to patient prognosis and immunotherapy in PRAD through cluster analysis. By utilizing diverse datasets and employing various machine learning methods for clustering, diagnostic models for PRAD were developed and validated. The random forest algorithm pinpointed HSPE1 as the most crucial prognostic gene among the stem cell-related genes. Furthermore, the study delved into the association between HSPE1 and immune infiltration, and employed molecular docking to investigate the relationship between HSPE1 and its associated compounds. Immunofluorescence staining analysis of 60 PRAD tissue samples confirmed the expression of HSPE1 and its correlation with patient prognosis in PRAD.

RESULT

This study identified 15 crucial stem cell-related genes through single-cell analysis, highlighting their importance in diagnosing, prognosticating, and potentially treating PRAD patients. HSPE1 was specifically linked to PRAD prognosis and response to immunotherapy, with experimental data supporting its upregulation in PRAD and association with poorer prognosis.

CONCLUSION

Overall, our findings underscore the significant role of stem cell-related genes in PRAD and unveil HSPE1 as a novel target related to stem cell.

摘要

背景

癌症干细胞(CSC)是肿瘤内具有自我更新能力并产生多种肿瘤细胞的细胞亚群。这些细胞在推动肿瘤转移、复发和对治疗的耐药性方面至关重要。本研究旨在确定与前列腺腺癌(PRAD)中的 CSC 相关的关键调节基因,并评估它们在 PRAD 患者的诊断、预后和免疫治疗中的潜在意义。

方法

本研究利用单细胞分析技术鉴定与干细胞相关的基因,并通过聚类分析评估它们与 PRAD 患者预后和免疫治疗的相关性。通过利用多个数据集和采用不同的聚类机器学习方法,为 PRAD 开发和验证了诊断模型。随机森林算法确定 HSPE1 是与干细胞相关基因中最关键的预后基因。此外,本研究还探讨了 HSPE1 与免疫浸润之间的关系,并通过分子对接研究了 HSPE1 与其相关化合物之间的关系。对 60 例 PRAD 组织样本的免疫荧光染色分析证实了 HSPE1 的表达及其与 PRAD 患者预后的相关性。

结果

本研究通过单细胞分析确定了 15 个关键的与干细胞相关的基因,强调了它们在诊断、预后和潜在治疗 PRAD 患者方面的重要性。HSPE1 与 PRAD 的预后和对免疫治疗的反应特别相关,实验数据支持其在 PRAD 中的上调,并与较差的预后相关。

结论

总体而言,我们的研究结果强调了与干细胞相关的基因在 PRAD 中的重要作用,并揭示了 HSPE1 作为与干细胞相关的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7e/11390519/2d0e7dad849f/fimmu-15-1464698-g001.jpg

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