目前，尚无关于USP31在透明细胞肾细胞癌（ccRCC）中的预后、潜在影响和治疗价值的研究。为了弥补这一空白，本研究旨在揭示USP31在ccRCC中的潜在作用和可能的机制。使用R软件对来自癌症基因组图谱（即KIRC）和基因表达组综合数据库的数据进行生物信息学分析。通过PCR验证了ccRCC中USP31的表达。通过Cox回归分析评估了USP31的独立预后能力。我们进行了基因集富集分析（GSEA）以探索与USP31相关的潜在通路。我们还通过ChEA3预测了USP31与免疫之间的关系可能通过上游转录因子（TFs）实现。在ccRCC中，USP31表达水平较高，且这种表达增加与不良预后相关（p < 0.05）。通过单变量和多变量Cox回归分析，确定了USP31作为ccRCC的独立预后因子（p < 0.05）。此外，通过GSEA鉴定出了8个与USP31相关的通路（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、免疫检查点和免疫浸润相关（p < 0.05）。此外，ccRCC中USP31表达高的患者在免疫治疗后显示出更好的治疗效果（p < 0.05）。最后，我们发现AR、USF1、MXI1和CLOCK可能是USP31的潜在上游转录因子。USP31可以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中的潜在TF-USP31 mRNA网络机制。© 2023 John Wiley & Sons Ltd.

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.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.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.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.© 2023 John Wiley & Sons Ltd.