Hu Weijing, Wu Bo, Chen Yongquan, Guo Xiaoling, Wang Xiaosong, Wang Dongwen
Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Sci Rep. 2025 Aug 13;15(1):29651. doi: 10.1038/s41598-025-15439-1.
Interleukin-2 Receptor Subunit Gamma (IL2RG) has been implicated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to explore IL2RG expression, its relationship with IL2RG -related lncRNAs (IRLs). Gene expression and clinical data for ccRCC were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus(GEO) database. The IRL signature was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Clinical data validated the diagnostic value of the signature. The prognostic value of the signal was assessed using Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curves. The prognostic value of the nomogram was further evaluated through calibration curves, ROC curves, and Decision Curve Analysis (DCA). Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), CIBERSORT algorithms, and TISCH2 database were applied to analyze immune function and immune cell infiltration in different risk groups. Clinical treatment differences among populations with varying risks and susceptibilities were predicted using R packages. The expression of IL2RG and key lncRNAs was validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). IL2RG was significantly upregulated in ccRCC tissues and correlated with advanced clinical stages (p < 0.001). High IL2RG expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) (p < 0.05). A 6-IRLs signature was identified, and the resulting model accurately predicted survival outcomes. Immune-related pathways were enriched in high-risk patients, and drug sensitivity analysis indicated that high-risk patients were more responsive to sunitinib and temsirolimus. IL2RG and its related 6-IRLs are potential biomarkers for ccRCC progression. The 6-IRLs model provides a robust tool for predicting prognosis and guiding therapeutic decisions.
白细胞介素-2受体γ亚基（IL2RG）与多种癌症有关，但其在肾透明细胞癌（ccRCC）中的作用尚不清楚。本研究旨在探讨IL2RG的表达及其与IL2RG相关长链非编码RNA（IRLs）的关系。从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取ccRCC的基因表达和临床数据。使用最小绝对收缩和选择算子（LASSO）回归分析构建IRL特征。临床数据验证了该特征的诊断价值。使用Kaplan-Meier分析和受试者工作特征（ROC）曲线评估该信号的预后价值。通过校准曲线、ROC曲线和决策曲线分析（DCA）进一步评估列线图的预后价值。应用基因集富集分析（GSEA）、单样本GSEA（ssGSEA）、CIBERSORT算法和TISCH2数据库分析不同风险组的免疫功能和免疫细胞浸润情况。使用R包预测不同风险和易感性人群的临床治疗差异。通过定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）验证IL2RG和关键长链非编码RNA的表达。IL2RG在ccRCC组织中显著上调，并与晚期临床分期相关（p < 0.001）。高IL2RG表达与较差的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）相关（p < 0.05）。鉴定出一个6-IRLs特征，所得模型准确预测了生存结果。免疫相关通路在高危患者中富集，药物敏感性分析表明高危患者对舒尼替尼和替西罗莫司更敏感。IL2RG及其相关的6-IRLs是ccRCC进展的潜在生物标志物。6-IRLs模型为预测预后和指导治疗决策提供了一个强大的工具。
