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单细胞和批量 RNA 测序揭示,有丝分裂相关基因 HAUS1 是预测前列腺腺癌 (PRAD) 预后和免疫反应的有前途的指标。

Single-cell and bulk RNA-sequencing reveals mitosis-involved gene HAUS1 is a promising indicator for predicting prognosis and immune responses in prostate adenocarcinoma (PRAD).

机构信息

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

出版信息

Cell Biol Int. 2024 Aug;48(8):1169-1184. doi: 10.1002/cbin.12191. Epub 2024 May 31.

DOI:10.1002/cbin.12191
PMID:38818762
Abstract

It was imperative to identify latent biomarkers pertinent to malignancies, given the pivotal role targeted molecular therapies play in tumor treatment investigations. This study aimed to assess the validity of HAUS1 as an indicator for survival prognosis and immune responses in prostate adenocarcinoma (PRAD) via single-cell and bulk RNA-sequencing. Related data on HAUS1 expression in PRAD were obtained from online databases, followed by comprehensive analyses to delineate its associations with survival prognosis, implicated pathways, and immune responses. Besides, the expression pattern of HAUS1 in PRAD was also verified in vitro, by using qRT-PCR, Western blot analysis, and immunohistochemistry. We found HAUS1 was downregulated in PRAD compared with normal tissues, as verified in vitro by qRT-PCR, Western blot, and immunohistochemistry (p < 0.05). Single-cell RNA-sequencing analysis indicated that HAUS1 had relatively higher expressions in B cells, Mono/Macro cells, and Endothelial cells compared with other cell types. Cox regression analysis revealed HAUS1 could serve as an independent indicator for the overall survival prognosis of PRAD (p < 0.05). Spearman correlation analyses revealed HAUS1 was closely related to the tumor microenvironment, immune cell infiltration levels, immune checkpoints, and immune cell pathways (p < 0.05). Furthermore, HAUS1 expression was found to be closely related to the immunotherapeutic response of patients receiving clinical intervention (p < 0.05). Collectively, our findings underscored the significant role of HAUS1 in PRAD prognosis and immune response, thereby presenting a novel and promising avenue for investigating the clinical utility of immunotherapy in PRAD.

摘要

鉴于靶向分子疗法在肿瘤治疗研究中起着关键作用,确定与恶性肿瘤相关的潜在生物标志物至关重要。本研究旨在通过单细胞和批量 RNA 测序评估 HAUS1 作为前列腺腺癌 (PRAD) 生存预后和免疫反应指标的有效性。从在线数据库中获得了关于 HAUS1 在 PRAD 中表达的相关数据,然后进行了全面分析,以描绘其与生存预后、涉及的途径和免疫反应的关联。此外,还通过 qRT-PCR、Western blot 分析和免疫组织化学在体外验证了 HAUS1 在 PRAD 中的表达模式。我们发现与正常组织相比,HAUS1 在 PRAD 中表达下调,这在体外通过 qRT-PCR、Western blot 和免疫组织化学得到了验证(p<0.05)。单细胞 RNA 测序分析表明,与其他细胞类型相比,HAUS1 在 B 细胞、Mono/Macro 细胞和内皮细胞中的表达相对较高。Cox 回归分析显示,HAUS1 可以作为 PRAD 总生存预后的独立指标(p<0.05)。Spearman 相关性分析显示,HAUS1 与肿瘤微环境、免疫细胞浸润水平、免疫检查点和免疫细胞途径密切相关(p<0.05)。此外,发现 HAUS1 的表达与接受临床干预的患者的免疫治疗反应密切相关(p<0.05)。总之,我们的研究结果强调了 HAUS1 在 PRAD 预后和免疫反应中的重要作用,从而为研究免疫疗法在 PRAD 中的临床应用提供了新的有前途的途径。

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