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USP31 可作为通过单细胞和批量 RNA 测序预测透明细胞肾细胞癌预后和免疫反应的潜在生物标志物。

USP31 serves as a potential biomarker for predicting prognosis and immune responses for clear cell renal cell carcinoma via single-cell and bulk RNA-sequencing.

机构信息

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

Laoximen Street Community Health Service Center, Huangpu District, Shanghai, China.

出版信息

J Gene Med. 2024 Jan;26(1):e3594. doi: 10.1002/jgm.3594. Epub 2023 Sep 12.

Abstract

BACKGROUND

Currently, there is no research available on the prognosis, potential effect and therapeutic value of USP31 in clear cell renal cell carcinoma (ccRCC). To address this gap, the present study aimed to shed light on its potential roles and possible mechanisms in ccRCC.

METHODS

R software was utilized to conduct bioinformatics analyses with the data derived from The Cancer Genome Atlas (i.e. KIRC) and Gene Expression Omnibus datasets. The expression of USP31 in ccRCC was validated by a PCR. The independent prognostic ability of USP31 was evaluated by Cox regression analysis. We conducted gene set enrichment analysis (GSEA) to explore the potential USP31-related pathways. We also discussed the relationships between USP31 and immunity, by predicting its possible upstream transcription factors (TFs) by ChEA3.

RESULTS

In ccRCC, USP31 demonstrated a high level of expression and this increased expression was correlated with a poor prognosis (p < 0.05). Through univariate and multivariate Cox regression analysis, USP31 was identified as an independent prognostic factor for ccRCC (p < 0.05). Furthermore, eight USP31-related pathways were identified by GSEA (p < 0.05). Moreover, USP31 was found to be associated with microsatellite instability, tumor microenvironment, a variety of immune cells and immune checkpoints and immune infiltration (p < 0.05). Additionally, Patients with high USP31 expression in ccRCC were shown to have better curative effects after immunotherapy (p < 0.05). Finally, we found that AR, USF1, MXI1 and CLOCK could be the potential upstream TFs of USP31.

CONCLUSIONS

USP31 could serve as a potential biomarker for predicting both prognosis and immune responses, revealing its potential mechanisms of TF-USP31 mRNA networks in ccRCC.

摘要

背景

目前,关于 USP31 在透明细胞肾细胞癌(ccRCC)中的预后、潜在作用和治疗价值尚无研究。为了填补这一空白,本研究旨在探讨其在 ccRCC 中的潜在作用和可能机制。

方法

利用 R 软件对来自癌症基因组图谱(即 KIRC)和基因表达综合数据库的数据集进行生物信息学分析。通过 PCR 验证 ccRCC 中 USP31 的表达。通过 Cox 回归分析评估 USP31 的独立预后能力。我们进行了基因集富集分析(GSEA)以探讨潜在的 USP31 相关途径。我们还通过 ChEA3 预测其可能的上游转录因子(TFs)来讨论 USP31 与免疫之间的关系。

结果

在 ccRCC 中,USP31 表达水平较高,且这种高表达与预后不良相关(p<0.05)。通过单因素和多因素 Cox 回归分析,USP31 被确定为 ccRCC 的独立预后因素(p<0.05)。此外,通过 GSEA 鉴定了 8 个与 USP31 相关的途径(p<0.05)。此外,发现 USP31 与微卫星不稳定性、肿瘤微环境、多种免疫细胞和免疫检查点以及免疫浸润有关(p<0.05)。此外,ccRCC 中高 USP31 表达的患者在免疫治疗后显示出更好的疗效(p<0.05)。最后,我们发现 AR、USF1、MXI1 和 CLOCK 可能是 USP31 的潜在上游 TFs。

结论

USP31 可作为预测预后和免疫反应的潜在生物标志物,揭示了其在 ccRCC 中 TF-USP31 mRNA 网络的潜在机制。

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